[{"acknowledgement":"We are grateful to Edwin Munro for their feedback and help with the single particle analysis. We thank members of the Heisenberg and Loose labs for their help and feedback on the manuscript, notably Xin Tong for making the PCS2-mCherry-AHPH plasmid. Finally, we thank the Aquatics and Imaging & Optics facilities of ISTA for their continuous support, especially Yann Cesbron for assistance with the laser cutter. This work was supported by an ERC\r\nAdvanced Grant (MECSPEC) to C.-P.H.","year":"2024","_id":"14795","page":"171-182.e8","oa_version":"Published Version","type":"journal_article","month":"01","abstract":[{"lang":"eng","text":"Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time plays a central role in cell-cell contact formation and maturation. Nevertheless, how this process is mechanistically achieved when new contacts are formed remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical F-actin flows, driven by the depletion of myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2 becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical tension gradient from the contact rim to its center. This tension gradient, in turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determines the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells."}],"date_updated":"2025-07-22T14:58:27Z","volume":34,"corr_author":"1","date_created":"2024-01-14T23:00:56Z","file_date_updated":"2024-01-16T10:53:31Z","status":"public","external_id":{"arxiv":["2410.03589"]},"intvolume":"        34","citation":{"ama":"Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. <i>Current Biology</i>. 2024;34(1):171-182.e8. doi:<a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">10.1016/j.cub.2023.11.067</a>","ista":"Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. 2024. Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. Current Biology. 34(1), 171–182.e8.","mla":"Arslan, Feyza N., et al. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell Contacts.” <i>Current Biology</i>, vol. 34, no. 1, Elsevier, 2024, p. 171–182.e8, doi:<a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">10.1016/j.cub.2023.11.067</a>.","apa":"Arslan, F. N., Hannezo, E. B., Merrin, J., Loose, M., &#38; Heisenberg, C.-P. J. (2024). Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. <i>Current Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">https://doi.org/10.1016/j.cub.2023.11.067</a>","ieee":"F. N. Arslan, E. B. Hannezo, J. Merrin, M. Loose, and C.-P. J. Heisenberg, “Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts,” <i>Current Biology</i>, vol. 34, no. 1. Elsevier, p. 171–182.e8, 2024.","chicago":"Arslan, Feyza N, Edouard B Hannezo, Jack Merrin, Martin Loose, and Carl-Philipp J Heisenberg. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell Contacts.” <i>Current Biology</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">https://doi.org/10.1016/j.cub.2023.11.067</a>.","short":"F.N. Arslan, E.B. Hannezo, J. Merrin, M. Loose, C.-P.J. Heisenberg, Current Biology 34 (2024) 171–182.e8."},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2024-01-08T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","department":[{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"MaLo"},{"_id":"NanoFab"}],"publication":"Current Biology","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"Yes (via OA deal)","ec_funded":1,"scopus_import":"1","author":[{"full_name":"Arslan, Feyza N","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5809-9566","last_name":"Arslan","first_name":"Feyza N"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo"},{"last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"first_name":"Martin","last_name":"Loose","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"}],"day":"08","file":[{"success":1,"file_name":"2024_CurrentBiology_Arslan.pdf","content_type":"application/pdf","relation":"main_file","file_size":5183861,"creator":"dernst","date_updated":"2024-01-16T10:53:31Z","file_id":"14813","checksum":"51220b76d72a614208f84bdbfbaf9b72","date_created":"2024-01-16T10:53:31Z","access_level":"open_access"}],"title":"Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts","arxiv":1,"project":[{"grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425"}],"issue":"1","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0960-9822"],"eissn":["1879-0445"]},"doi":"10.1016/j.cub.2023.11.067","quality_controlled":"1"},{"intvolume":"        14","citation":{"ama":"Ucar MC, Hannezo EB, Tiilikainen E, et al. Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>. 2023;14. doi:<a href=\"https://doi.org/10.1038/s41467-023-41456-7\">10.1038/s41467-023-41456-7</a>","mla":"Ucar, Mehmet C., et al. “Self-Organized and Directed Branching Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>, vol. 14, 5878, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41467-023-41456-7\">10.1038/s41467-023-41456-7</a>.","ista":"Ucar MC, Hannezo EB, Tiilikainen E, Liaqat I, Jakobsson E, Nurmi H, Vaahtomeri K. 2023. Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. Nature Communications. 14, 5878.","apa":"Ucar, M. C., Hannezo, E. B., Tiilikainen, E., Liaqat, I., Jakobsson, E., Nurmi, H., &#38; Vaahtomeri, K. (2023). Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-023-41456-7\">https://doi.org/10.1038/s41467-023-41456-7</a>","ieee":"M. C. Ucar <i>et al.</i>, “Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks,” <i>Nature Communications</i>, vol. 14. Springer Nature, 2023.","chicago":"Ucar, Mehmet C, Edouard B Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma Jakobsson, Harri Nurmi, and Kari Vaahtomeri. “Self-Organized and Directed Branching Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41467-023-41456-7\">https://doi.org/10.1038/s41467-023-41456-7</a>.","short":"M.C. Ucar, E.B. Hannezo, E. Tiilikainen, I. Liaqat, E. Jakobsson, H. Nurmi, K. Vaahtomeri, Nature Communications 14 (2023)."},"status":"public","external_id":{"isi":["001075884500007"],"pmid":["37735168"]},"date_published":"2023-09-21T00:00:00Z","ddc":["570"],"publication_status":"published","oa":1,"has_accepted_license":"1","_id":"14378","acknowledgement":"We thank Dr. Kari Alitalo (University of Helsinki and Wihuri Research Institute) for critical reading of the manuscript, providing Vegfc+/− and Clp24ΔEC mouse strains and for hosting K.V.’s Academy of Finland postdoctoral researcher period (2015–2018). We thank Dr. Sara Wickström (University of Helsinki and Wihuri Research Institute) for providing Sox9:Egfp mouse\r\nstrain and the discussions. We thank Maija Atuegwu and Tapio Tainola for technical assistance. This work received funding from the Academy of Finland (K.V., 315710), Sigrid Juselius Foundation (K.V.), University of Helsinki (K.V.), Wihuri Research Institute (K.V.), the ERC under the European Union’s Horizon 2020 research and innovation program (grant agreement\r\nNo. 851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411 (to M.C.U.). Part of the work was carried out with the support of HiLIFE Laboratory Animal Centre Core Facility, University of Helsinki, Finland. Imaging was performed at the Biomedicum Imaging Unit, Helsinki University, Helsinki, Finland, with the support of Biocenter Finland. The AAVpreparations were produced at the Helsinki Virus (HelVi) Core.","year":"2023","volume":14,"file_date_updated":"2023-10-03T07:46:36Z","date_created":"2023-10-01T22:01:13Z","type":"journal_article","month":"09","oa_version":"Published Version","date_updated":"2023-12-13T12:31:05Z","abstract":[{"text":"Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization.","lang":"eng"}],"isi":1,"language":[{"iso":"eng"}],"project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"doi":"10.1038/s41467-023-41456-7","quality_controlled":"1","publication_identifier":{"eissn":["2041-1723"]},"publication":"Nature Communications","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"article_processing_charge":"Yes","scopus_import":"1","publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"EdHa"}],"pmid":1,"article_number":"5878","title":"Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks","author":[{"orcid":"0000-0003-0506-4217","id":"50B2A802-6007-11E9-A42B-EB23E6697425","full_name":"Ucar, Mehmet C","first_name":"Mehmet C","last_name":"Ucar"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo"},{"full_name":"Tiilikainen, Emmi","first_name":"Emmi","last_name":"Tiilikainen"},{"last_name":"Liaqat","first_name":"Inam","full_name":"Liaqat, Inam"},{"full_name":"Jakobsson, Emma","first_name":"Emma","last_name":"Jakobsson"},{"full_name":"Nurmi, Harri","first_name":"Harri","last_name":"Nurmi"},{"full_name":"Vaahtomeri, Kari","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","first_name":"Kari","last_name":"Vaahtomeri"}],"day":"21","file":[{"file_size":8143264,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_name":"2023_NatureComm_Ucar.pdf","success":1,"date_created":"2023-10-03T07:46:36Z","access_level":"open_access","file_id":"14384","date_updated":"2023-10-03T07:46:36Z","checksum":"4fe5423403f2531753bcd9e0fea48e05"}]},{"title":"Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics","article_number":"e3002315","file":[{"date_created":"2023-10-16T07:20:49Z","access_level":"open_access","date_updated":"2023-10-16T07:20:49Z","file_id":"14431","checksum":"40a2b11b41d70a0e5939f8a52b66e389","content_type":"application/pdf","relation":"main_file","file_size":6193110,"creator":"dernst","success":1,"file_name":"2023_PloSBiology_Unterweger.pdf"}],"day":"04","author":[{"first_name":"Iris A.","last_name":"Unterweger","full_name":"Unterweger, Iris A."},{"full_name":"Klepstad, Julie","last_name":"Klepstad","first_name":"Julie"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Lundegaard","first_name":"Pia R.","full_name":"Lundegaard, Pia R."},{"last_name":"Trusina","first_name":"Ala","full_name":"Trusina, Ala"},{"full_name":"Ober, Elke A.","last_name":"Ober","first_name":"Elke A."}],"scopus_import":"1","article_processing_charge":"No","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publication":"PLoS Biology","department":[{"_id":"EdHa"}],"publisher":"Public Library of Science","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","doi":"10.1371/journal.pbio.3002315","publication_identifier":{"eissn":["1545-7885"]},"language":[{"iso":"eng"}],"issue":"10","project":[{"grant_number":"851288","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E"}],"date_created":"2023-10-15T22:01:10Z","file_date_updated":"2023-10-16T07:20:49Z","volume":21,"abstract":[{"text":"To meet the physiological demands of the body, organs need to establish a functional tissue architecture and adequate size as the embryo develops to adulthood. In the liver, uni- and bipotent progenitor differentiation into hepatocytes and biliary epithelial cells (BECs), and their relative proportions, comprise the functional architecture. Yet, the contribution of individual liver progenitors at the organ level to both fates, and their specific proportion, is unresolved. Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is established (i) fast, (ii) solely by heterogeneous lineage decisions from uni- and bipotent progenitors, and (iii) independent of subsequent cell type–specific proliferation. Extending lineage tracing to adulthood determined that embryonic cells undergo spatially heterogeneous three-dimensional growth associated with distinct environments. Strikingly, giant clusters comprising almost half a ventral lobe suggest lobe-specific dominant-like growth behaviours. We show substantial hepatocyte polyploidy in juveniles representing another hallmark of postembryonic liver growth. Our findings uncover heterogeneous progenitor contributions to tissue architecture-defining cell type proportions and postembryonic organ growth as key mechanisms forming the adult liver.","lang":"eng"}],"date_updated":"2023-10-16T07:25:48Z","month":"10","oa_version":"Published Version","type":"journal_article","_id":"14426","year":"2023","acknowledgement":"We thank the Ober group for discussion and comments on the manuscript. We are grateful to\r\nDr. F. Lemaigre for feedback on the manuscript and Dr. T. Piotrowski for invaluable support.\r\nWe thank the department of experimental medicine (AEM) in Copenhagen for expert fish\r\ncare. We gratefully acknowledge the DanStem Imaging Platform (University of Copenhagen)\r\nfor support and assistance in this work.\r\nThis work is supported by Novo Nordisk Foundation grant NNF17CC0027852 (EAO);\r\nNordisk Foundation grant NNF19OC0058327 (EAO); Novo Nordisk Foundation grant\r\nNNF17OC0031204 (PRL); https://novonordiskfonden.dk/en/; Danish National\r\nResearch Foundation grant DNRF116 (EAO and AT); https://dg.dk/en/; John and Birthe Meyer\r\nFoundation (PRL) and European Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme Grant Agreement No. 851288 (EH).","ddc":["570"],"date_published":"2023-10-04T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"ama":"Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS Biology</i>. 2023;21(10). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002315\">10.1371/journal.pbio.3002315</a>","apa":"Unterweger, I. A., Klepstad, J., Hannezo, E. B., Lundegaard, P. R., Trusina, A., &#38; Ober, E. A. (2023). Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002315\">https://doi.org/10.1371/journal.pbio.3002315</a>","mla":"Unterweger, Iris A., et al. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS Biology</i>, vol. 21, no. 10, e3002315, Public Library of Science, 2023, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002315\">10.1371/journal.pbio.3002315</a>.","ista":"Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. 2023. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. PLoS Biology. 21(10), e3002315.","chicago":"Unterweger, Iris A., Julie Klepstad, Edouard B Hannezo, Pia R. Lundegaard, Ala Trusina, and Elke A. Ober. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS Biology</i>. Public Library of Science, 2023. <a href=\"https://doi.org/10.1371/journal.pbio.3002315\">https://doi.org/10.1371/journal.pbio.3002315</a>.","ieee":"I. A. Unterweger, J. Klepstad, E. B. Hannezo, P. R. Lundegaard, A. Trusina, and E. A. Ober, “Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics,” <i>PLoS Biology</i>, vol. 21, no. 10. Public Library of Science, 2023.","short":"I.A. Unterweger, J. Klepstad, E.B. Hannezo, P.R. Lundegaard, A. Trusina, E.A. Ober, PLoS Biology 21 (2023)."},"related_material":{"link":[{"url":"https://github.com/JulieKlepstad/LiverDevelopment","relation":"software"}]},"intvolume":"        21","status":"public"},{"department":[{"_id":"MaLo"},{"_id":"EdHa"},{"_id":"JoDa"}],"year":"2023","acknowledgement":"This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L., B. P.M.  was also supported by the Kanazawa University WPI- NanoLSI Bio-SPM collaborative research program. Z.D. has received funding from Doctoral Programme of the Austrian Academy of Sciences (OeAW): Grant agreement 26360. We thank Jan Brugues (MPI CBG, Dresden, Germany), Andela Saric (ISTA, Klosterneuburg, Austria), Daniel Pearce (Uni Geneva, Switzerland) for valuable scientific input and comments on the manuscript. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). ","publisher":"Institute of Science and Technology Austria","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"article_processing_charge":"No","_id":"13116","month":"07","type":"research_data","oa_version":"Published Version","file":[{"file_size":13111,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"main_file","creator":"pradler","file_name":"ReadMe 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emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ -- a prokaryotic homologue of the eukaryotic protein tubulin -- polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here, we connect single filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram captures these features quantitatively, demonstrating how the flexibility, density and chirality of active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division. 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Dunajova <i>et al.</i>, “Chiral and nematic phases of flexible active filaments.” Institute of Science and Technology Austria, 2023.","short":"Z. Dunajova, B. Prats Mateu, P. Radler, K. Lim, D. Brandis, P. Velicky, J.G. Danzl, R.W. Wong, J. Elgeti, E.B. Hannezo, M. Loose, (2023).","ama":"Dunajova Z, Prats Mateu B, Radler P, et al. Chiral and nematic phases of flexible active filaments. 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13116\">10.15479/AT:ISTA:13116</a>","apa":"Dunajova, Z., Prats Mateu, B., Radler, P., Lim, K., Brandis, D., Velicky, P., … Loose, M. (2023). Chiral and nematic phases of flexible active filaments. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:13116\">https://doi.org/10.15479/AT:ISTA:13116</a>","ista":"Dunajova Z, Prats Mateu B, Radler P, Lim K, Brandis D, Velicky P, Danzl JG, Wong RW, Elgeti J, Hannezo EB, Loose M. 2023. Chiral and nematic phases of flexible active filaments, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:13116\">10.15479/AT:ISTA:13116</a>.","mla":"Dunajova, Zuzana, et al. <i>Chiral and Nematic Phases of Flexible Active Filaments</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13116\">10.15479/AT:ISTA:13116</a>."},"related_material":{"record":[{"relation":"used_in_publication","id":"13314","status":"public"}]},"has_accepted_license":"1","oa":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"date_published":"2023-07-26T00:00:00Z","doi":"10.15479/AT:ISTA:13116","ddc":["539"]},{"has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"ddc":["530"],"date_published":"2023-12-01T00:00:00Z","external_id":{"pmid":["38075437"]},"status":"public","citation":{"ieee":"Z. Dunajova <i>et al.</i>, “Chiral and nematic phases of flexible active filaments,” <i>Nature Physics</i>, vol. 19. Springer Nature, pp. 1916–1926, 2023.","chicago":"Dunajova, Zuzana, Batirtze Prats Mateu, Philipp Radler, Keesiang Lim, Dörte Brandis, Philipp Velicky, Johann G Danzl, et al. “Chiral and Nematic Phases of Flexible Active Filaments.” <i>Nature Physics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41567-023-02218-w\">https://doi.org/10.1038/s41567-023-02218-w</a>.","short":"Z. Dunajova, B. Prats Mateu, P. Radler, K. Lim, D. Brandis, P. Velicky, J.G. Danzl, R.W. Wong, J. Elgeti, E.B. Hannezo, M. Loose, Nature Physics 19 (2023) 1916–1926.","ama":"Dunajova Z, Prats Mateu B, Radler P, et al. Chiral and nematic phases of flexible active filaments. <i>Nature Physics</i>. 2023;19:1916-1926. doi:<a href=\"https://doi.org/10.1038/s41567-023-02218-w\">10.1038/s41567-023-02218-w</a>","ista":"Dunajova Z, Prats Mateu B, Radler P, Lim K, Brandis D, Velicky P, Danzl JG, Wong RW, Elgeti J, Hannezo EB, Loose M. 2023. Chiral and nematic phases of flexible active filaments. Nature Physics. 19, 1916–1926.","mla":"Dunajova, Zuzana, et al. “Chiral and Nematic Phases of Flexible Active Filaments.” <i>Nature Physics</i>, vol. 19, Springer Nature, 2023, pp. 1916–26, doi:<a href=\"https://doi.org/10.1038/s41567-023-02218-w\">10.1038/s41567-023-02218-w</a>.","apa":"Dunajova, Z., Prats Mateu, B., Radler, P., Lim, K., Brandis, D., Velicky, P., … Loose, M. (2023). Chiral and nematic phases of flexible active filaments. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-023-02218-w\">https://doi.org/10.1038/s41567-023-02218-w</a>"},"related_material":{"record":[{"relation":"research_data","status":"public","id":"13116"}]},"intvolume":"        19","abstract":[{"lang":"eng","text":"The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ—a prokaryotic homologue of the eukaryotic protein tubulin—polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here we connect single-filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that the density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram quantitatively captures these features, demonstrating how the flexibility, density and chirality of the active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division."}],"date_updated":"2024-02-21T12:19:08Z","oa_version":"Published Version","type":"journal_article","month":"12","page":"1916-1926","file_date_updated":"2024-01-30T14:28:30Z","date_created":"2023-07-27T14:44:45Z","volume":19,"year":"2023","acknowledgement":"This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L., B. P.M. was also supported by the Kanazawa University WPI- NanoLSI Bio-SPM collaborative research program. Z.D. has received funding from Doctoral Programme of the Austrian Academy of Sciences (OeAW): Grant agreement 26360. We thank Jan Brugues (MPI CBG, Dresden, Germany), Andela Saric (ISTA, Klosterneuburg, Austria), Daniel Pearce (Uni Geneva, Switzerland) for valuable scientific input and comments on the manuscript. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF).","_id":"13314","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"quality_controlled":"1","doi":"10.1038/s41567-023-02218-w","project":[{"grant_number":"679239","_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Self-Organization of the Bacterial Cell"},{"grant_number":"P34607","name":"Understanding bacterial cell division by in vitro\r\nreconstitution","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d"},{"name":"Motile active matter models of migrating cells and chiral filaments","_id":"34d75525-11ca-11ed-8bc3-89b6307fee9d","grant_number":"26360"}],"language":[{"iso":"eng"}],"file":[{"file_name":"2023_NaturePhysics_Dunajova.pdf","success":1,"creator":"dernst","file_size":22471673,"relation":"main_file","content_type":"application/pdf","checksum":"bc7673ca07d37309013a86166577b2f7","file_id":"14916","date_updated":"2024-01-30T14:28:30Z","access_level":"open_access","date_created":"2024-01-30T14:28:30Z"}],"day":"01","author":[{"first_name":"Zuzana","last_name":"Dunajova","full_name":"Dunajova, Zuzana","id":"4B39F286-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Prats Mateu, Batirtze","id":"299FE892-F248-11E8-B48F-1D18A9856A87","first_name":"Batirtze","last_name":"Prats Mateu"},{"last_name":"Radler","first_name":"Philipp","full_name":"Radler, Philipp","orcid":"0000-0001-9198-2182 ","id":"40136C2A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Lim","first_name":"Keesiang","full_name":"Lim, Keesiang"},{"last_name":"Brandis","first_name":"Dörte","full_name":"Brandis, Dörte","id":"21d64d35-f128-11eb-9611-b8bcca7a12fd"},{"full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","first_name":"Philipp"},{"last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Wong, Richard W.","last_name":"Wong","first_name":"Richard W."},{"first_name":"Jens","last_name":"Elgeti","full_name":"Elgeti, Jens"},{"full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo"},{"full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","last_name":"Loose","first_name":"Martin"}],"title":"Chiral and nematic phases of flexible active filaments","pmid":1,"department":[{"_id":"JoDa"},{"_id":"EdHa"},{"_id":"MaLo"},{"_id":"GradSch"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","scopus_import":"1","article_processing_charge":"Yes (in subscription journal)","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publication":"Nature Physics"},{"_id":"13971","year":"2023","acknowledgement":"D.G. and J.P. thank E. Krasnopeeva, C. Guet, G. Guessous and T. Hwa for providing the E. coli strains. This material is based upon work supported by the US Department of Energy under award DE-SC0019769. I.P. acknowledges funding by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie Grant Agreement No. 101034413. A.Š. acknowledges funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (Grant No. 802960). M.C.U. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie Grant Agreement No. 754411.","date_created":"2023-08-06T22:01:11Z","file_date_updated":"2024-01-30T12:26:08Z","volume":19,"abstract":[{"lang":"eng","text":"When in equilibrium, thermal forces agitate molecules, which then diffuse, collide and bind to form materials. However, the space of accessible structures in which micron-scale particles can be organized by thermal forces is limited, owing to the slow dynamics and metastable states. Active agents in a passive fluid generate forces and flows, forming a bath with active fluctuations. Two unanswered questions are whether those active agents can drive the assembly of passive components into unconventional states and which material properties they will exhibit. Here we show that passive, sticky beads immersed in a bath of swimming Escherichia coli bacteria aggregate into unconventional clusters and gels that are controlled by the activity of the bath. We observe a slow but persistent rotation of the aggregates that originates in the chirality of the E. coli flagella and directs aggregation into structures that are not accessible thermally. We elucidate the aggregation mechanism with a numerical model of spinning, sticky beads and reproduce quantitatively the experimental results. We show that internal activity controls the phase diagram and the structure of the aggregates. Overall, our results highlight the promising role of active baths in designing the structural and mechanical properties of materials with unconventional phases."}],"date_updated":"2024-01-30T12:26:55Z","oa_version":"Published Version","type":"journal_article","month":"11","page":"1680-1688","citation":{"ama":"Grober D, Palaia I, Ucar MC, Hannezo EB, Šarić A, Palacci JA. Unconventional colloidal aggregation in chiral bacterial baths. <i>Nature Physics</i>. 2023;19:1680-1688. doi:<a href=\"https://doi.org/10.1038/s41567-023-02136-x\">10.1038/s41567-023-02136-x</a>","ista":"Grober D, Palaia I, Ucar MC, Hannezo EB, Šarić A, Palacci JA. 2023. Unconventional colloidal aggregation in chiral bacterial baths. Nature Physics. 19, 1680–1688.","mla":"Grober, Daniel, et al. “Unconventional Colloidal Aggregation in Chiral Bacterial Baths.” <i>Nature Physics</i>, vol. 19, Springer Nature, 2023, pp. 1680–88, doi:<a href=\"https://doi.org/10.1038/s41567-023-02136-x\">10.1038/s41567-023-02136-x</a>.","apa":"Grober, D., Palaia, I., Ucar, M. C., Hannezo, E. B., Šarić, A., &#38; Palacci, J. A. (2023). Unconventional colloidal aggregation in chiral bacterial baths. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-023-02136-x\">https://doi.org/10.1038/s41567-023-02136-x</a>","ieee":"D. Grober, I. Palaia, M. C. Ucar, E. B. Hannezo, A. Šarić, and J. A. Palacci, “Unconventional colloidal aggregation in chiral bacterial baths,” <i>Nature Physics</i>, vol. 19. Springer Nature, pp. 1680–1688, 2023.","chicago":"Grober, Daniel, Ivan Palaia, Mehmet C Ucar, Edouard B Hannezo, Anđela Šarić, and Jérémie A Palacci. “Unconventional Colloidal Aggregation in Chiral Bacterial Baths.” <i>Nature Physics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41567-023-02136-x\">https://doi.org/10.1038/s41567-023-02136-x</a>.","short":"D. Grober, I. Palaia, M.C. Ucar, E.B. Hannezo, A. Šarić, J.A. Palacci, Nature Physics 19 (2023) 1680–1688."},"intvolume":"        19","external_id":{"isi":["001037346400005"]},"status":"public","ddc":["530"],"date_published":"2023-11-01T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"published","article_processing_charge":"Yes","scopus_import":"1","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publication":"Nature Physics","department":[{"_id":"EdHa"},{"_id":"AnSa"},{"_id":"JePa"}],"publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Unconventional colloidal aggregation in chiral bacterial baths","file":[{"date_updated":"2024-01-30T12:26:08Z","file_id":"14906","checksum":"7e282c2ebc0ac82125a04f6b4742d4c1","date_created":"2024-01-30T12:26:08Z","access_level":"open_access","success":1,"file_name":"2023_NaturePhysics_Grober.pdf","relation":"main_file","content_type":"application/pdf","file_size":6365607,"creator":"dernst"}],"day":"01","author":[{"first_name":"Daniel","last_name":"Grober","id":"abdfc56f-34fb-11ee-bd33-fd766fce5a99","full_name":"Grober, Daniel"},{"last_name":"Palaia","first_name":"Ivan","full_name":"Palaia, Ivan","id":"9c805cd2-4b75-11ec-a374-db6dd0ed57fa","orcid":" 0000-0002-8843-9485 "},{"id":"50B2A802-6007-11E9-A42B-EB23E6697425","orcid":"0000-0003-0506-4217","full_name":"Ucar, Mehmet C","last_name":"Ucar","first_name":"Mehmet C"},{"orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B"},{"full_name":"Šarić, Anđela","orcid":"0000-0002-7854-2139","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","last_name":"Šarić","first_name":"Anđela"},{"full_name":"Palacci, Jérémie A","id":"8fb92548-2b22-11eb-b7c1-a3f0d08d7c7d","orcid":"0000-0002-7253-9465","last_name":"Palacci","first_name":"Jérémie A"}],"language":[{"iso":"eng"}],"isi":1,"project":[{"name":"IST-BRIDGE: International postdoctoral program","call_identifier":"H2020","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","grant_number":"101034413"},{"grant_number":"802960","name":"Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines","call_identifier":"H2020","_id":"eba2549b-77a9-11ec-83b8-a81e493eae4e"},{"name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411"}],"quality_controlled":"1","doi":"10.1038/s41567-023-02136-x","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]}},{"main_file_link":[{"url":"https://doi.org/10.1126/sciimmunol.adc9584","open_access":"1"}],"date_published":"2023-09-01T00:00:00Z","publication_status":"published","oa":1,"citation":{"ieee":"J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol. 8, no. 87. American Association for the Advancement of Science, 2023.","chicago":"Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz, Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>. American Association for the Advancement of Science, 2023. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>.","short":"J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B. Hannezo, M.K. Sixt, Science Immunology 8 (2023).","ama":"Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. 2023;8(87). doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>","ista":"Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB, Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 8(87), adc9584.","mla":"Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>.","apa":"Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin, J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>"},"intvolume":"         8","related_material":{"record":[{"relation":"research_data","status":"public","id":"14279"},{"id":"14697","status":"public","relation":"dissertation_contains"}]},"external_id":{"isi":["001062110600003"],"pmid":["37656776"]},"status":"public","date_created":"2023-09-06T08:07:51Z","volume":8,"abstract":[{"lang":"eng","text":"Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization."}],"date_updated":"2023-12-21T14:30:01Z","month":"09","type":"journal_article","oa_version":"Published Version","_id":"14274","year":"2023","acknowledgement":"We thank I. de Vries and the Scientific Service Units (Life Sciences, Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute of Science and Technology Austria for excellent support, as well as all the rotation students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis work was supported by grants from the European Research Council under the European Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20) to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411.","quality_controlled":"1","doi":"10.1126/sciimmunol.adc9584","publication_identifier":{"issn":["2470-9468"]},"language":[{"iso":"eng"}],"issue":"87","isi":1,"keyword":["General Medicine","Immunology"],"project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients","grant_number":"724373"},{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"},{"grant_number":"W01250-B20","name":"Nano-Analytics of Cellular Systems","_id":"265E2996-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"title":"CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration","article_number":"adc9584","day":"01","author":[{"full_name":"Alanko, Jonna H","orcid":"0000-0002-7698-3061","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","last_name":"Alanko","first_name":"Jonna H"},{"last_name":"Ucar","first_name":"Mehmet C","orcid":"0000-0003-0506-4217","id":"50B2A802-6007-11E9-A42B-EB23E6697425","full_name":"Ucar, Mehmet C"},{"last_name":"Canigova","first_name":"Nikola","id":"3795523E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8518-5926","full_name":"Canigova, Nikola"},{"last_name":"Stopp","first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","full_name":"Stopp, Julian A"},{"full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Jan"},{"first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo"},{"last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"article_processing_charge":"No","ec_funded":1,"scopus_import":"1","article_type":"original","publication":"Science Immunology","pmid":1,"department":[{"_id":"MiSi"},{"_id":"EdHa"},{"_id":"NanoFab"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"American Association for the Advancement of Science"},{"file":[{"file_id":"14335","date_updated":"2023-09-15T06:30:50Z","checksum":"f881d98c89eb9f1aa136d7b781511553","date_created":"2023-09-15T06:30:50Z","access_level":"open_access","file_name":"2023_PRXLife_Boocock.pdf","success":1,"file_size":2559520,"relation":"main_file","content_type":"application/pdf","creator":"dernst"}],"day":"20","author":[{"full_name":"Boocock, Daniel R","orcid":"0000-0002-1585-2631","id":"453AF628-F248-11E8-B48F-1D18A9856A87","first_name":"Daniel R","last_name":"Boocock"},{"full_name":"Hirashima, Tsuyoshi","first_name":"Tsuyoshi","last_name":"Hirashima"},{"last_name":"Hannezo","first_name":"Edouard B","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"}],"title":"Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers","article_number":"013001","department":[{"_id":"EdHa"}],"publisher":"American Physical Society","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ec_funded":1,"article_processing_charge":"Yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publication":"PRX Life","publication_identifier":{"issn":["2835-8279"]},"quality_controlled":"1","doi":"10.1103/prxlife.1.013001","project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"}],"language":[{"iso":"eng"}],"issue":"1","date_updated":"2023-09-15T06:39:17Z","abstract":[{"text":"Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signaling pathways. Either feature alone can give rise to complex emergent phenomena, for example, mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological materials. We address this in Madin-Darby canine kidney (MDCK) monolayers, considering both mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from a uniform active glass to periodic spatiotemporal waves. We parametrize the model from published experimental data sets on MDCK monolayers and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves produce feedback on one another and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves at both the local and global levels.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","month":"07","date_created":"2023-09-06T08:30:59Z","file_date_updated":"2023-09-15T06:30:50Z","volume":1,"year":"2023","acknowledgement":"We thank all members of the Hannezo group for discussions and suggestions, as well as Sound Wai Phow for technical assistance. This work received funding from the European Research Council under the EU Horizon 2020 research and innovation program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and the Ministry of Education under the Research Centres of Excellence program through the MBI at NUS.","_id":"14277","has_accepted_license":"1","oa":1,"publication_status":"published","ddc":["570"],"date_published":"2023-07-20T00:00:00Z","status":"public","citation":{"ama":"Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. <i>PRX Life</i>. 2023;1(1). doi:<a href=\"https://doi.org/10.1103/prxlife.1.013001\">10.1103/prxlife.1.013001</a>","ista":"Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001.","mla":"Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” <i>PRX Life</i>, vol. 1, no. 1, 013001, American Physical Society, 2023, doi:<a href=\"https://doi.org/10.1103/prxlife.1.013001\">10.1103/prxlife.1.013001</a>.","apa":"Boocock, D. R., Hirashima, T., &#38; Hannezo, E. B. (2023). Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. <i>PRX Life</i>. American Physical Society. <a href=\"https://doi.org/10.1103/prxlife.1.013001\">https://doi.org/10.1103/prxlife.1.013001</a>","ieee":"D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers,” <i>PRX Life</i>, vol. 1, no. 1. American Physical Society, 2023.","chicago":"Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” <i>PRX Life</i>. American Physical Society, 2023. <a href=\"https://doi.org/10.1103/prxlife.1.013001\">https://doi.org/10.1103/prxlife.1.013001</a>.","short":"D.R. Boocock, T. Hirashima, E.B. Hannezo, PRX Life 1 (2023)."},"intvolume":"         1"},{"citation":{"short":"B. Corominas-Murtra, E.B. Hannezo, Seminars in Cell &#38; Developmental Biology 150–151 (2023) 58–65.","ieee":"B. Corominas-Murtra and E. B. Hannezo, “Modelling the dynamics of mammalian gut homeostasis,” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151. Elsevier, pp. 58–65, 2023.","chicago":"Corominas-Murtra, Bernat, and Edouard B Hannezo. “Modelling the Dynamics of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">https://doi.org/10.1016/j.semcdb.2022.11.005</a>.","mla":"Corominas-Murtra, Bernat, and Edouard B. Hannezo. “Modelling the Dynamics of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151, Elsevier, 2023, pp. 58–65, doi:<a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">10.1016/j.semcdb.2022.11.005</a>.","ista":"Corominas-Murtra B, Hannezo EB. 2023. Modelling the dynamics of mammalian gut homeostasis. Seminars in Cell &#38; Developmental Biology. 150–151, 58–65.","apa":"Corominas-Murtra, B., &#38; Hannezo, E. B. (2023). Modelling the dynamics of mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">https://doi.org/10.1016/j.semcdb.2022.11.005</a>","ama":"Corominas-Murtra B, Hannezo EB. Modelling the dynamics of mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>. 2023;150-151:58-65. doi:<a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">10.1016/j.semcdb.2022.11.005</a>"},"external_id":{"pmid":["36470715"],"isi":["001053522200001"]},"status":"public","date_published":"2023-12-02T00:00:00Z","ddc":["570"],"has_accepted_license":"1","publication_status":"published","oa":1,"_id":"12162","year":"2023","acknowledgement":"This work received funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 851288 to E.H.).\r\nB. C-M wants to acknowledge the support of the field of excellence Complexity of Life, in Basic Research and Innovation of the University of Graz.","file_date_updated":"2024-01-08T10:16:04Z","date_created":"2023-01-12T12:09:47Z","volume":"150-151","type":"journal_article","oa_version":"Published Version","month":"12","date_updated":"2024-01-16T13:22:32Z","abstract":[{"lang":"eng","text":"Homeostatic balance in the intestinal epithelium relies on a fast cellular turnover, which is coordinated by an intricate interplay between biochemical signalling, mechanical forces and organ geometry. We review recent modelling approaches that have been developed to understand different facets of this remarkable homeostatic equilibrium. Existing models offer different, albeit complementary, perspectives on the problem. First, biomechanical models aim to explain the local and global mechanical stresses driving cell renewal as well as tissue shape maintenance. Second, compartmental models provide insights into the conditions necessary to keep a constant flow of cells with well-defined ratios of cell types, and how perturbations can lead to an unbalance of relative compartment sizes. A third family of models address, at the cellular level, the nature and regulation of stem fate choices that are necessary to fuel cellular turnover. We also review how these different approaches are starting to be integrated together across scales, to provide quantitative predictions and new conceptual frameworks to think about the dynamics of cell renewal in complex tissues."}],"page":"58-65","language":[{"iso":"eng"}],"keyword":["Cell Biology","Developmental Biology"],"isi":1,"project":[{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}],"quality_controlled":"1","doi":"10.1016/j.semcdb.2022.11.005","publication_identifier":{"issn":["1084-9521"]},"article_type":"review","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"Yes (via OA deal)","scopus_import":"1","ec_funded":1,"publication":"Seminars in Cell & Developmental Biology","department":[{"_id":"EdHa"}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","title":"Modelling the dynamics of mammalian gut homeostasis","file":[{"success":1,"file_name":"2023_SeminarsCellDevBiology_CorominasMurtra.pdf","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":1343750,"checksum":"c619887cf130f4649bf3035417186004","date_updated":"2024-01-08T10:16:04Z","file_id":"14741","access_level":"open_access","date_created":"2024-01-08T10:16:04Z"}],"day":"02","author":[{"last_name":"Corominas-Murtra","first_name":"Bernat","full_name":"Corominas-Murtra, Bernat","id":"43BE2298-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9806-5643"},{"last_name":"Hannezo","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B"}]},{"year":"2023","_id":"12428","page":"183-205","date_updated":"2023-02-03T10:58:56Z","abstract":[{"text":"The mammary gland consists of a bilayered epithelial structure with an extensively branched morphology. The majority of this epithelial tree is laid down during puberty, during which actively proliferating terminal end buds repeatedly elongate and bifurcate to form the basic structure of the ductal tree. Mammary ducts consist of a basal and luminal cell layer with a multitude of identified sub-lineages within both layers. The understanding of how these different cell lineages are cooperatively driving branching morphogenesis is a problem of crossing multiple scales, as this requires information on the macroscopic branched structure of the gland, as well as data on single-cell dynamics driving the morphogenic program. Here we describe a method to combine genetic lineage tracing with whole-gland branching analysis. Quantitative data on the global organ structure can be used to derive a model for mammary gland branching morphogenesis and provide a backbone on which the dynamics of individual cell lineages can be simulated and compared to lineage-tracing approaches. Eventually, these quantitative models and experiments allow to understand the couplings between the macroscopic shape of the mammary gland and the underlying single-cell dynamics driving branching morphogenesis.","lang":"eng"}],"month":"01","oa_version":"Published Version","type":"book_chapter","volume":2608,"file_date_updated":"2023-02-03T10:56:39Z","date_created":"2023-01-29T23:00:58Z","alternative_title":["Methods in Molecular Biology"],"editor":[{"full_name":"Margadant, Coert","last_name":"Margadant","first_name":"Coert"}],"status":"public","external_id":{"pmid":["36653709"]},"intvolume":"      2608","citation":{"ama":"Hannezo EB, Scheele CLGJ. A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland. In: Margadant C, ed. <i>Cell Migration in Three Dimensions</i>. Vol 2608. MIMB. Springer Nature; 2023:183-205. doi:<a href=\"https://doi.org/10.1007/978-1-0716-2887-4_12\">10.1007/978-1-0716-2887-4_12</a>","ista":"Hannezo EB, Scheele CLGJ. 2023.A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland. In: Cell Migration in Three Dimensions. Methods in Molecular Biology, vol. 2608, 183–205.","mla":"Hannezo, Edouard B., and Colinda L. G. J. Scheele. “A Guide Toward Multi-Scale and Quantitative Branching Analysis in the Mammary Gland.” <i>Cell Migration in Three Dimensions</i>, edited by Coert Margadant, vol. 2608, Springer Nature, 2023, pp. 183–205, doi:<a href=\"https://doi.org/10.1007/978-1-0716-2887-4_12\">10.1007/978-1-0716-2887-4_12</a>.","apa":"Hannezo, E. B., &#38; Scheele, C. L. G. J. (2023). A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland. In C. Margadant (Ed.), <i>Cell Migration in Three Dimensions</i> (Vol. 2608, pp. 183–205). Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-2887-4_12\">https://doi.org/10.1007/978-1-0716-2887-4_12</a>","ieee":"E. B. Hannezo and C. L. G. J. Scheele, “A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland,” in <i>Cell Migration in Three Dimensions</i>, vol. 2608, C. Margadant, Ed. Springer Nature, 2023, pp. 183–205.","chicago":"Hannezo, Edouard B, and Colinda L.G.J. Scheele. “A Guide Toward Multi-Scale and Quantitative Branching Analysis in the Mammary Gland.” In <i>Cell Migration in Three Dimensions</i>, edited by Coert Margadant, 2608:183–205. MIMB. Springer Nature, 2023. <a href=\"https://doi.org/10.1007/978-1-0716-2887-4_12\">https://doi.org/10.1007/978-1-0716-2887-4_12</a>.","short":"E.B. Hannezo, C.L.G.J. Scheele, in:, C. Margadant (Ed.), Cell Migration in Three Dimensions, Springer Nature, 2023, pp. 183–205."},"oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2023-01-19T00:00:00Z","ddc":["570"],"publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"department":[{"_id":"EdHa"}],"publication":"Cell Migration in Three Dimensions","article_processing_charge":"No","scopus_import":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Scheele, Colinda L.G.J.","last_name":"Scheele","first_name":"Colinda L.G.J."}],"file":[{"creator":"dernst","relation":"main_file","content_type":"application/pdf","file_size":826598,"success":1,"file_name":"2023_MIMB_Hannezo.pdf","access_level":"open_access","date_created":"2023-02-03T10:56:39Z","checksum":"aec1b8d3ba938ddf9d8fcb777f3c38ee","date_updated":"2023-02-03T10:56:39Z","file_id":"12500"}],"day":"19","title":"A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland","series_title":"MIMB","language":[{"iso":"eng"}],"publication_identifier":{"isbn":["9781071628867"],"eissn":["1940-6029"],"eisbn":["9781071628874"]},"doi":"10.1007/978-1-0716-2887-4_12","quality_controlled":"1"},{"file":[{"creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":2898063,"success":1,"file_name":"2023_AdvancedMaterials_Schamberger.pdf","access_level":"open_access","date_created":"2023-09-26T10:51:56Z","checksum":"5c04d68130e97a0ecd1ca27fbc15a246","date_updated":"2023-09-26T10:51:56Z","file_id":"14373"}],"day":"29","author":[{"first_name":"Barbara","last_name":"Schamberger","full_name":"Schamberger, Barbara"},{"full_name":"Ziege, Ricardo","last_name":"Ziege","first_name":"Ricardo"},{"full_name":"Anselme, Karine","last_name":"Anselme","first_name":"Karine"},{"first_name":"Martine","last_name":"Ben Amar","full_name":"Ben Amar, Martine"},{"first_name":"Michał","last_name":"Bykowski","full_name":"Bykowski, Michał"},{"full_name":"Castro, André P.G.","first_name":"André P.G.","last_name":"Castro"},{"full_name":"Cipitria, Amaia","first_name":"Amaia","last_name":"Cipitria"},{"full_name":"Coles, Rhoslyn A.","first_name":"Rhoslyn A.","last_name":"Coles"},{"first_name":"Rumiana","last_name":"Dimova","full_name":"Dimova, Rumiana"},{"last_name":"Eder","first_name":"Michaela","full_name":"Eder, Michaela"},{"full_name":"Ehrig, Sebastian","last_name":"Ehrig","first_name":"Sebastian"},{"full_name":"Escudero, Luis M.","first_name":"Luis M.","last_name":"Escudero"},{"full_name":"Evans, Myfanwy E.","first_name":"Myfanwy E.","last_name":"Evans"},{"first_name":"Paulo R.","last_name":"Fernandes","full_name":"Fernandes, Paulo R."},{"last_name":"Fratzl","first_name":"Peter","full_name":"Fratzl, Peter"},{"first_name":"Liesbet","last_name":"Geris","full_name":"Geris, Liesbet"},{"full_name":"Gierlinger, Notburga","last_name":"Gierlinger","first_name":"Notburga"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo"},{"first_name":"Aleš","last_name":"Iglič","full_name":"Iglič, Aleš"},{"full_name":"Kirkensgaard, Jacob J.K.","last_name":"Kirkensgaard","first_name":"Jacob J.K."},{"full_name":"Kollmannsberger, Philip","last_name":"Kollmannsberger","first_name":"Philip"},{"first_name":"Łucja","last_name":"Kowalewska","full_name":"Kowalewska, Łucja"},{"first_name":"Nicholas A.","last_name":"Kurniawan","full_name":"Kurniawan, Nicholas A."},{"full_name":"Papantoniou, Ioannis","last_name":"Papantoniou","first_name":"Ioannis"},{"full_name":"Pieuchot, Laurent","last_name":"Pieuchot","first_name":"Laurent"},{"full_name":"Pires, Tiago H.V.","first_name":"Tiago H.V.","last_name":"Pires"},{"full_name":"Renner, Lars D.","first_name":"Lars D.","last_name":"Renner"},{"last_name":"Sageman-Furnas","first_name":"Andrew O.","full_name":"Sageman-Furnas, Andrew O."},{"full_name":"Schröder-Turk, Gerd E.","last_name":"Schröder-Turk","first_name":"Gerd E."},{"last_name":"Sengupta","first_name":"Anupam","full_name":"Sengupta, Anupam"},{"full_name":"Sharma, Vikas R.","last_name":"Sharma","first_name":"Vikas R."},{"first_name":"Antonio","last_name":"Tagua","full_name":"Tagua, Antonio"},{"last_name":"Tomba","first_name":"Caterina","full_name":"Tomba, Caterina"},{"last_name":"Trepat","first_name":"Xavier","full_name":"Trepat, Xavier"},{"first_name":"Sarah L.","last_name":"Waters","full_name":"Waters, Sarah L."},{"last_name":"Yeo","first_name":"Edwina F.","full_name":"Yeo, Edwina F."},{"first_name":"Andreas","last_name":"Roschger","full_name":"Roschger, Andreas"},{"full_name":"Bidan, Cécile M.","last_name":"Bidan","first_name":"Cécile M."},{"last_name":"Dunlop","first_name":"John W.C.","full_name":"Dunlop, John W.C."}],"title":"Curvature in biological systems: Its quantification, emergence, and implications across the scales","article_number":"2206110","pmid":1,"department":[{"_id":"EdHa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Wiley","scopus_import":"1","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"review","publication":"Advanced Materials","publication_identifier":{"eissn":["1521-4095"],"issn":["0935-9648"]},"quality_controlled":"1","doi":"10.1002/adma.202206110","language":[{"iso":"eng"}],"issue":"13","isi":1,"date_updated":"2023-09-26T10:56:46Z","abstract":[{"lang":"eng","text":"Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, the interplay between the distribution of morphogens or micro-organisms and the emergence of curvature across length scales is addressed with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by-product of the chemical, biological, and mechanical processes but that curvature acts also as a signal that co-determines these processes."}],"type":"journal_article","oa_version":"Published Version","month":"03","date_created":"2023-03-05T23:01:06Z","file_date_updated":"2023-09-26T10:51:56Z","volume":35,"year":"2023","acknowledgement":"B.S. and A.R. contributed equally to this work. A.P.G.C. and P.R.F. acknowledge the funding from Fundação para a Ciência e Tecnologia (Portugal), through IDMEC, under LAETA project UIDB/50022/2020. T.H.V.P. acknowledges the funding from Fundação para a Ciência e Tecnologia (Portugal), through Ph.D. Grant 2020.04417.BD. A.S. acknowledges that this work was partially supported by the ATTRACT Investigator Grant (no. A17/MS/11572821/MBRACE, to A.S.) from the Luxembourg National Research Fund. The author thanks Gerardo Ceada for his help in the graphical representations. N.A.K. acknowledges support from the European Research Council (grant 851960) and the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). M.B.A. acknowledges support from the French National Research Agency (grant ANR-201-8-CE1-3-0008 for the project “Epimorph”). G.E.S.T. acknowledges funding by the Australian Research Council through project DP200102593. A.C. acknowledges the funding from the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Grant CI 203/-2 1, the Spanish Ministry of Science and Innovation (PID2021-123013O-BI00) and the IKERBASQUE Basque Foundation for Science.","_id":"12710","has_accepted_license":"1","publication_status":"published","oa":1,"ddc":["570"],"date_published":"2023-03-29T00:00:00Z","external_id":{"isi":["000941068900001"],"pmid":["36461812"]},"status":"public","citation":{"apa":"Schamberger, B., Ziege, R., Anselme, K., Ben Amar, M., Bykowski, M., Castro, A. P. G., … Dunlop, J. W. C. (2023). Curvature in biological systems: Its quantification, emergence, and implications across the scales. <i>Advanced Materials</i>. Wiley. <a href=\"https://doi.org/10.1002/adma.202206110\">https://doi.org/10.1002/adma.202206110</a>","mla":"Schamberger, Barbara, et al. “Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales.” <i>Advanced Materials</i>, vol. 35, no. 13, 2206110, Wiley, 2023, doi:<a href=\"https://doi.org/10.1002/adma.202206110\">10.1002/adma.202206110</a>.","ista":"Schamberger B, Ziege R, Anselme K, Ben Amar M, Bykowski M, Castro APG, Cipitria A, Coles RA, Dimova R, Eder M, Ehrig S, Escudero LM, Evans ME, Fernandes PR, Fratzl P, Geris L, Gierlinger N, Hannezo EB, Iglič A, Kirkensgaard JJK, Kollmannsberger P, Kowalewska Ł, Kurniawan NA, Papantoniou I, Pieuchot L, Pires THV, Renner LD, Sageman-Furnas AO, Schröder-Turk GE, Sengupta A, Sharma VR, Tagua A, Tomba C, Trepat X, Waters SL, Yeo EF, Roschger A, Bidan CM, Dunlop JWC. 2023. Curvature in biological systems: Its quantification, emergence, and implications across the scales. Advanced Materials. 35(13), 2206110.","ama":"Schamberger B, Ziege R, Anselme K, et al. Curvature in biological systems: Its quantification, emergence, and implications across the scales. <i>Advanced Materials</i>. 2023;35(13). doi:<a href=\"https://doi.org/10.1002/adma.202206110\">10.1002/adma.202206110</a>","short":"B. Schamberger, R. Ziege, K. Anselme, M. Ben Amar, M. Bykowski, A.P.G. Castro, A. Cipitria, R.A. Coles, R. Dimova, M. Eder, S. Ehrig, L.M. Escudero, M.E. Evans, P.R. Fernandes, P. Fratzl, L. Geris, N. Gierlinger, E.B. Hannezo, A. Iglič, J.J.K. Kirkensgaard, P. Kollmannsberger, Ł. Kowalewska, N.A. Kurniawan, I. Papantoniou, L. Pieuchot, T.H.V. Pires, L.D. Renner, A.O. Sageman-Furnas, G.E. Schröder-Turk, A. Sengupta, V.R. Sharma, A. Tagua, C. Tomba, X. Trepat, S.L. Waters, E.F. Yeo, A. Roschger, C.M. Bidan, J.W.C. Dunlop, Advanced Materials 35 (2023).","chicago":"Schamberger, Barbara, Ricardo Ziege, Karine Anselme, Martine Ben Amar, Michał Bykowski, André P.G. Castro, Amaia Cipitria, et al. “Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales.” <i>Advanced Materials</i>. Wiley, 2023. <a href=\"https://doi.org/10.1002/adma.202206110\">https://doi.org/10.1002/adma.202206110</a>.","ieee":"B. Schamberger <i>et al.</i>, “Curvature in biological systems: Its quantification, emergence, and implications across the scales,” <i>Advanced Materials</i>, vol. 35, no. 13. Wiley, 2023."},"intvolume":"        35"},{"acknowledgement":"We thank S. Hippenmeyer for the reagents and C. P. Heisenberg, J. Briscoe and K. Page for comments on the manuscript. This work was supported by IST Austria; the European Research Council under Horizon 2020 research and innovation programme grant no. 680037 and Horizon Europe grant 101044579 (A.K.); Austrian Science Fund (FWF): F78 (Stem Cell Modulation) (A.K.); ISTFELLOW postdoctoral program (A.S.); Narodowe Centrum Nauki, Poland SONATA, 2017/26/D/NZ2/00454 (M.Z.); and the Polish National Agency for Academic Exchange (M.Z.).","year":"2023","_id":"12837","page":"1050-1058","month":"07","oa_version":"Published Version","type":"journal_article","date_updated":"2023-10-04T11:14:05Z","abstract":[{"lang":"eng","text":"As developing tissues grow in size and undergo morphogenetic changes, their material properties may be altered. Such changes result from tension dynamics at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms controlling the physical state of growing tissues are unclear. We found that at early developmental stages, the epithelium in the developing mouse spinal cord maintains both high junctional tension and high fluidity. This is achieved via a mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the cell proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification uncovered here resembles a glass transition that depends on the dynamical stresses generated by proliferation and differentiation. Our finding that the fluidity of developing epithelia is linked to interkinetic nuclear movements and the dynamics of growth is likely to be relevant to multiple developing tissues."}],"volume":19,"file_date_updated":"2023-10-04T11:13:28Z","date_created":"2023-04-16T22:01:09Z","external_id":{"isi":["000964029300003"]},"status":"public","related_material":{"record":[{"status":"public","id":"13081","relation":"dissertation_contains"}]},"intvolume":"        19","citation":{"ama":"Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. <i>Nature Physics</i>. 2023;19:1050-1058. doi:<a href=\"https://doi.org/10.1038/s41567-023-01977-w\">10.1038/s41567-023-01977-w</a>","mla":"Bocanegra, Laura, et al. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” <i>Nature Physics</i>, vol. 19, Springer Nature, 2023, pp. 1050–58, doi:<a href=\"https://doi.org/10.1038/s41567-023-01977-w\">10.1038/s41567-023-01977-w</a>.","ista":"Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. 2023. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. 19, 1050–1058.","apa":"Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., &#38; Kicheva, A. (2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-023-01977-w\">https://doi.org/10.1038/s41567-023-01977-w</a>","ieee":"L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell cycle dynamics control fluidity of the developing mouse neuroepithelium,” <i>Nature Physics</i>, vol. 19. Springer Nature, pp. 1050–1058, 2023.","chicago":"Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” <i>Nature Physics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41567-023-01977-w\">https://doi.org/10.1038/s41567-023-01977-w</a>.","short":"L. Bocanegra, A. Singh, E.B. Hannezo, M.P. Zagórski, A. Kicheva, Nature Physics 19 (2023) 1050–1058."},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2023-07-01T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","department":[{"_id":"EdHa"},{"_id":"AnKi"}],"publication":"Nature Physics","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","ec_funded":1,"article_processing_charge":"No","author":[{"last_name":"Bocanegra","first_name":"Laura","id":"4896F754-F248-11E8-B48F-1D18A9856A87","full_name":"Bocanegra, Laura"},{"full_name":"Singh, Amrita","id":"76250f9f-3a21-11eb-9a80-a6180a0d7958","first_name":"Amrita","last_name":"Singh"},{"first_name":"Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B"},{"last_name":"Zagórski","first_name":"Marcin P","id":"343DA0DC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7896-7762","full_name":"Zagórski, Marcin P"},{"last_name":"Kicheva","first_name":"Anna","orcid":"0000-0003-4509-4998","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","full_name":"Kicheva, Anna"}],"file":[{"access_level":"open_access","date_created":"2023-10-04T11:13:28Z","checksum":"858225a4205b74406e5045006cdd853f","date_updated":"2023-10-04T11:13:28Z","file_id":"14392","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":5532285,"success":1,"file_name":"2023_NaturePhysics_Boncanegra.pdf"}],"day":"01","title":"Cell cycle dynamics control fluidity of the developing mouse neuroepithelium","project":[{"grant_number":"680037","call_identifier":"H2020","_id":"B6FC0238-B512-11E9-945C-1524E6697425","name":"Coordination of Patterning And Growth In the Spinal Cord"},{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","name":"Mechanisms of tissue size regulation in spinal cord development","grant_number":"101044579"},{"grant_number":"F07802","_id":"059DF620-7A3F-11EA-A408-12923DDC885E","name":"Morphogen control of growth and pattern in the spinal cord"},{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"doi":"10.1038/s41567-023-01977-w","quality_controlled":"1"},{"pmid":1,"department":[{"_id":"EdHa"},{"_id":"CaHe"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Cell Press","scopus_import":"1","article_processing_charge":"No","article_type":"original","publication":"Trends in Cell Biology","day":"01","author":[{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B"},{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"title":"Rigidity transitions in development and disease","language":[{"iso":"eng"}],"issue":"5","isi":1,"publication_identifier":{"issn":["0962-8924"],"eissn":["1879-3088"]},"quality_controlled":"1","doi":"10.1016/j.tcb.2021.12.006","year":"2022","acknowledgement":"We thank present and former members of the Heisenberg and Hannezo groups, in particular Bernat Corominas-Murtra and Nicoletta Petridou, for helpful discussions, and Claudia Flandoli for the artwork. We apologize for not being able to cite a number of highly relevant studies, to stay within the maximum allowed number of citations.","_id":"10705","abstract":[{"lang":"eng","text":"Although rigidity and jamming transitions have been widely studied in physics and material science, their importance in a number of biological processes, including embryo development, tissue homeostasis, wound healing, and disease progression, has only begun to be recognized in the past few years. The hypothesis that biological systems can undergo rigidity/jamming transitions is attractive, as it would allow these systems to change their material properties rapidly and strongly. However, whether such transitions indeed occur in biological systems, how they are being regulated, and what their physiological relevance might be, is still being debated. Here, we review theoretical and experimental advances from the past few years, focusing on the regulation and role of potential tissue rigidity transitions in different biological processes."}],"date_updated":"2023-08-02T14:03:53Z","oa_version":"None","type":"journal_article","month":"05","page":"P433-444","date_created":"2022-01-30T23:01:34Z","volume":32,"external_id":{"isi":["000795773900009"],"pmid":["35058104"]},"status":"public","citation":{"chicago":"Hannezo, Edouard B, and Carl-Philipp J Heisenberg. “Rigidity Transitions in Development and Disease.” <i>Trends in Cell Biology</i>. Cell Press, 2022. <a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">https://doi.org/10.1016/j.tcb.2021.12.006</a>.","ieee":"E. B. Hannezo and C.-P. J. Heisenberg, “Rigidity transitions in development and disease,” <i>Trends in Cell Biology</i>, vol. 32, no. 5. Cell Press, pp. P433-444, 2022.","short":"E.B. Hannezo, C.-P.J. Heisenberg, Trends in Cell Biology 32 (2022) P433-444.","ama":"Hannezo EB, Heisenberg C-PJ. Rigidity transitions in development and disease. <i>Trends in Cell Biology</i>. 2022;32(5):P433-444. doi:<a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">10.1016/j.tcb.2021.12.006</a>","apa":"Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2022). Rigidity transitions in development and disease. <i>Trends in Cell Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">https://doi.org/10.1016/j.tcb.2021.12.006</a>","mla":"Hannezo, Edouard B., and Carl-Philipp J. Heisenberg. “Rigidity Transitions in Development and Disease.” <i>Trends in Cell Biology</i>, vol. 32, no. 5, Cell Press, 2022, pp. P433-444, doi:<a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">10.1016/j.tcb.2021.12.006</a>.","ista":"Hannezo EB, Heisenberg C-PJ. 2022. Rigidity transitions in development and disease. Trends in Cell Biology. 32(5), P433-444."},"intvolume":"        32","publication_status":"published","date_published":"2022-05-01T00:00:00Z"},{"ddc":["570"],"date_published":"2022-02-22T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"       185","citation":{"short":"A. Yanagida, E. Corujo-Simon, C.K. Revell, P. Sahu, G.G. Stirparo, I.M. Aspalter, A.K. Winkel, R. Peters, H. De Belly, D.A.D. Cassani, S. Achouri, R. Blumenfeld, K. Franze, E.B. Hannezo, E.K. Paluch, J. Nichols, K.J. Chalut, Cell 185 (2022) 777–793.e20.","ieee":"A. Yanagida <i>et al.</i>, “Cell surface fluctuations regulate early embryonic lineage sorting,” <i>Cell</i>, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022.","chicago":"Yanagida, Ayaka, Elena Corujo-Simon, Christopher K. Revell, Preeti Sahu, Giuliano G. Stirparo, Irene M. Aspalter, Alex K. Winkel, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>. Cell Press, 2022. <a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">https://doi.org/10.1016/j.cell.2022.01.022</a>.","ista":"Yanagida A, Corujo-Simon E, Revell CK, Sahu P, Stirparo GG, Aspalter IM, Winkel AK, Peters R, De Belly H, Cassani DAD, Achouri S, Blumenfeld R, Franze K, Hannezo EB, Paluch EK, Nichols J, Chalut KJ. 2022. Cell surface fluctuations regulate early embryonic lineage sorting. Cell. 185(5), 777–793.e20.","mla":"Yanagida, Ayaka, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20, doi:<a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">10.1016/j.cell.2022.01.022</a>.","apa":"Yanagida, A., Corujo-Simon, E., Revell, C. K., Sahu, P., Stirparo, G. G., Aspalter, I. M., … Chalut, K. J. (2022). Cell surface fluctuations regulate early embryonic lineage sorting. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">https://doi.org/10.1016/j.cell.2022.01.022</a>","ama":"Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate early embryonic lineage sorting. <i>Cell</i>. 2022;185(5):777-793.e20. doi:<a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">10.1016/j.cell.2022.01.022</a>"},"status":"public","external_id":{"pmid":["35196500"],"isi":["000796293700007"]},"volume":185,"file_date_updated":"2022-03-07T07:55:23Z","date_created":"2022-03-06T23:01:52Z","page":"777-793.e20","abstract":[{"text":"In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages.","lang":"eng"}],"date_updated":"2023-08-02T14:43:50Z","oa_version":"Published Version","month":"02","type":"journal_article","_id":"10825","acknowledgement":"We are grateful to H. Niwa for Dox regulatable PB vector; G. Charras for EzrinT567D cDNA; K. Jones for tdTomato ESCs, R26-Confetti ESCs, and laboratory assistance; M. Kinoshita for pPB-CAG-H2B-BFP plasmid; P. Humphreys and D. Clements for imaging support; G. Chu, P. Attlesey, and staff for animal husbandry; S. Pallett for laboratory assistance; C. Mulas for critical feedback on the project; T. Boroviak for single-cell RNA-seq; the EMBL Genomics Core Facility for sequencing; and M. Merkel for developing and sharing the original version of the 3D Voronoi code. This work was financially supported by BBSRC ( BB/Moo4023/1 and BB/T007044/1 to K.J.C. and J.N., Alert16 grant BB/R000042 to E.K.P.), Leverhulme Trust ( RPG-2014-080 to K.J.C. and J.N.), European Research Council ( 772798 -CellFateTech to K.J.C., 311637 -MorphoCorDiv and 820188 -NanoMechShape to E.K.P., Starting Grant 851288 to E.H., and 772426 -MeChemGui to K.F.), the Isaac Newton Trust (to E.K.P.), Medical Research Council UK (MRC program award MC_UU_00012/5 to E.K.P.), the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 641639 ( ITN Biopol , H.D.B. and E.K.P.), the Alexander von Humboldt Foundation (Alexander von Humboldt Professorship to K.F.), EMBO ALTF 522-2021 (to P.S.), Centre for Trophoblast Research (Next Generation fellowship to S.A.), and JSPS Overseas Research Fellowships (to A.Y.). The Wellcome-MRC Cambridge Stem Cell Institute receives core funding from Wellcome Trust ( 203151/Z/16/Z ) and MRC ( MC_PC_17230 ). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","year":"2022","doi":"10.1016/j.cell.2022.01.022","quality_controlled":"1","publication_identifier":{"issn":["00928674"],"eissn":["10974172"]},"isi":1,"language":[{"iso":"eng"}],"issue":"5","project":[{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis"}],"title":"Cell surface fluctuations regulate early embryonic lineage sorting","author":[{"first_name":"Ayaka","last_name":"Yanagida","full_name":"Yanagida, Ayaka"},{"first_name":"Elena","last_name":"Corujo-Simon","full_name":"Corujo-Simon, Elena"},{"last_name":"Revell","first_name":"Christopher K.","full_name":"Revell, Christopher K."},{"last_name":"Sahu","first_name":"Preeti","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E","full_name":"Sahu, Preeti"},{"last_name":"Stirparo","first_name":"Giuliano G.","full_name":"Stirparo, Giuliano G."},{"full_name":"Aspalter, Irene M.","first_name":"Irene M.","last_name":"Aspalter"},{"first_name":"Alex K.","last_name":"Winkel","full_name":"Winkel, Alex K."},{"first_name":"Ruby","last_name":"Peters","full_name":"Peters, Ruby"},{"last_name":"De Belly","first_name":"Henry","full_name":"De Belly, Henry"},{"full_name":"Cassani, Davide A.D.","first_name":"Davide A.D.","last_name":"Cassani"},{"last_name":"Achouri","first_name":"Sarra","full_name":"Achouri, Sarra"},{"first_name":"Raphael","last_name":"Blumenfeld","full_name":"Blumenfeld, Raphael"},{"last_name":"Franze","first_name":"Kristian","full_name":"Franze, Kristian"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"last_name":"Paluch","first_name":"Ewa K.","full_name":"Paluch, Ewa K."},{"first_name":"Jennifer","last_name":"Nichols","full_name":"Nichols, Jennifer"},{"full_name":"Chalut, Kevin J.","last_name":"Chalut","first_name":"Kevin J."}],"day":"22","file":[{"creator":"dernst","file_size":8478995,"relation":"main_file","content_type":"application/pdf","file_name":"2022_Cell_Yanagida.pdf","success":1,"access_level":"open_access","date_created":"2022-03-07T07:55:23Z","checksum":"ae305060e8031297771b89dae9e36a29","file_id":"10831","date_updated":"2022-03-07T07:55:23Z"}],"publication":"Cell","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publisher":"Cell Press","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"EdHa"}]},{"author":[{"first_name":"Diana C","last_name":"Nunes Pinheiro","id":"2E839F16-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4333-7503","full_name":"Nunes Pinheiro, Diana C"},{"id":"4039350E-F248-11E8-B48F-1D18A9856A87","full_name":"Kardos, Roland","last_name":"Kardos","first_name":"Roland"},{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"day":"01","file":[{"file_name":"2022_NaturePhysics_Pinheiro.pdf","success":1,"file_size":36703569,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"12412","date_updated":"2023-01-27T07:32:01Z","checksum":"c86a8e8d80d1bfc46d56a01e88a2526a","date_created":"2023-01-27T07:32:01Z","access_level":"open_access"}],"title":"Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming","publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"publication":"Nature Physics","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"doi":"10.1038/s41567-022-01787-6","quality_controlled":"1","project":[{"grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation"},{"grant_number":"ALTF 850-2017","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","_id":"26520D1E-B435-11E9-9278-68D0E5697425"},{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"},{"grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"isi":1,"keyword":["General Physics and Astronomy"],"language":[{"iso":"eng"}],"issue":"12","page":"1482-1493","abstract":[{"lang":"eng","text":"Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis."}],"date_updated":"2023-08-04T09:15:58Z","oa_version":"Published Version","type":"journal_article","month":"12","volume":18,"date_created":"2023-01-16T09:45:19Z","file_date_updated":"2023-01-27T07:32:01Z","acknowledgement":"We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the manuscript. We also thank the members of the Heisenberg group, in particular A. Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging and Life Science facilities at IST\r\nAustria for continuous support. We thank C. Flandoli for the artwork in the figures. This work was supported by postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the European Union (European Research Council starting grant 851288 to É.H. and European Research Council advanced grant 742573 to C.-P.H.).","year":"2022","_id":"12209","oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2022-12-01T00:00:00Z","ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"external_id":{"isi":["000871319900002"]},"status":"public","intvolume":"        18","citation":{"ama":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. <i>Nature Physics</i>. 2022;18(12):1482-1493. doi:<a href=\"https://doi.org/10.1038/s41567-022-01787-6\">10.1038/s41567-022-01787-6</a>","apa":"Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-022-01787-6\">https://doi.org/10.1038/s41567-022-01787-6</a>","ista":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 18(12), 1482–1493.","mla":"Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>, vol. 18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:<a href=\"https://doi.org/10.1038/s41567-022-01787-6\">10.1038/s41567-022-01787-6</a>.","chicago":"Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41567-022-01787-6\">https://doi.org/10.1038/s41567-022-01787-6</a>.","ieee":"D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming,” <i>Nature Physics</i>, vol. 18, no. 12. Springer Nature, pp. 1482–1493, 2022.","short":"D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 18 (2022) 1482–1493."}},{"has_accepted_license":"1","publication_status":"published","oa":1,"ddc":["570"],"date_published":"2022-09-05T00:00:00Z","status":"public","external_id":{"isi":["000850348400025"]},"citation":{"ieee":"S. Randriamanantsoa <i>et al.</i>, “Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","chicago":"Randriamanantsoa, S., A. Papargyriou, H. C. Maurer, K. Peschke, M. Schuster, G. Zecchin, K. Steiger, et al. “Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32806-y\">https://doi.org/10.1038/s41467-022-32806-y</a>.","short":"S. Randriamanantsoa, A. Papargyriou, H.C. Maurer, K. Peschke, M. Schuster, G. Zecchin, K. Steiger, R. Öllinger, D. Saur, C. Scheel, R. Rad, E.B. Hannezo, M. Reichert, A.R. Bausch, Nature Communications 13 (2022).","ama":"Randriamanantsoa S, Papargyriou A, Maurer HC, et al. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32806-y\">10.1038/s41467-022-32806-y</a>","ista":"Randriamanantsoa S, Papargyriou A, Maurer HC, Peschke K, Schuster M, Zecchin G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch AR. 2022. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. Nature Communications. 13, 5219.","mla":"Randriamanantsoa, S., et al. “Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids.” <i>Nature Communications</i>, vol. 13, 5219, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32806-y\">10.1038/s41467-022-32806-y</a>.","apa":"Randriamanantsoa, S., Papargyriou, A., Maurer, H. C., Peschke, K., Schuster, M., Zecchin, G., … Bausch, A. R. (2022). Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32806-y\">https://doi.org/10.1038/s41467-022-32806-y</a>"},"related_material":{"record":[{"status":"public","id":"13068","relation":"research_data"}]},"intvolume":"        13","oa_version":"Published Version","type":"journal_article","month":"09","abstract":[{"lang":"eng","text":"The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis."}],"date_updated":"2023-08-04T09:25:23Z","date_created":"2023-01-16T09:46:53Z","file_date_updated":"2023-01-27T08:14:48Z","volume":13,"year":"2022","acknowledgement":"A.R.B. acknowledges the financial support of the European Research Council (ERC) through the funding of the grant Principles of Integrin Mechanics and Adhesion (PoINT) and the German Research Foundation (DFG, SFB 1032, project ID 201269156). E.H. was supported by the European Union (European Research Council Starting Grant 851288). D.S., M.R., and R.R. acknowledge the support by the German Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project S01, project ID 329628492). C.S. and M.R. acknowledge the support by the German Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project 12, project ID 329628492). M.R. was supported by the German Research Foundation (DFG RE 3723/4-1). A.P. and M.R. were supported by the German Cancer Aid (Max-Eder Program 111273 and 70114328).\r\nOpen Access funding enabled and organized by Projekt DEAL.","_id":"12217","publication_identifier":{"issn":["2041-1723"]},"quality_controlled":"1","doi":"10.1038/s41467-022-32806-y","project":[{"name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","grant_number":"851288"}],"language":[{"iso":"eng"}],"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"isi":1,"day":"05","file":[{"access_level":"open_access","date_created":"2023-01-27T08:14:48Z","checksum":"295261b5172274fd5b8f85a6a6058828","date_updated":"2023-01-27T08:14:48Z","file_id":"12416","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":22645149,"success":1,"file_name":"2022_NatureCommunications_Randriamanantsoa.pdf"}],"author":[{"full_name":"Randriamanantsoa, S.","last_name":"Randriamanantsoa","first_name":"S."},{"full_name":"Papargyriou, A.","first_name":"A.","last_name":"Papargyriou"},{"full_name":"Maurer, H. C.","first_name":"H. C.","last_name":"Maurer"},{"full_name":"Peschke, K.","last_name":"Peschke","first_name":"K."},{"last_name":"Schuster","first_name":"M.","full_name":"Schuster, M."},{"first_name":"G.","last_name":"Zecchin","full_name":"Zecchin, G."},{"first_name":"K.","last_name":"Steiger","full_name":"Steiger, K."},{"last_name":"Öllinger","first_name":"R.","full_name":"Öllinger, R."},{"first_name":"D.","last_name":"Saur","full_name":"Saur, D."},{"first_name":"C.","last_name":"Scheel","full_name":"Scheel, C."},{"full_name":"Rad, R.","first_name":"R.","last_name":"Rad"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","first_name":"Edouard B"},{"full_name":"Reichert, M.","first_name":"M.","last_name":"Reichert"},{"full_name":"Bausch, A. R.","first_name":"A. R.","last_name":"Bausch"}],"article_number":"5219","title":"Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids","department":[{"_id":"EdHa"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"article_processing_charge":"No","scopus_import":"1","publication":"Nature Communications"},{"article_number":"eadd2488","title":"A self-generated Toddler gradient guides mesodermal cell migration","author":[{"last_name":"Stock","first_name":"Jessica","full_name":"Stock, Jessica"},{"first_name":"Tomas","last_name":"Kazmar","full_name":"Kazmar, Tomas"},{"full_name":"Schlumm, Friederike","last_name":"Schlumm","first_name":"Friederike"},{"last_name":"Hannezo","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B"},{"full_name":"Pauli, Andrea","last_name":"Pauli","first_name":"Andrea"}],"file":[{"file_name":"2022_ScienceAdvances_Stock.pdf","success":1,"file_size":1636732,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"12444","date_updated":"2023-01-30T09:27:49Z","checksum":"f59cdb824e5d4221045def81f46f6c65","date_created":"2023-01-30T09:27:49Z","access_level":"open_access"}],"day":"14","publication":"Science Advances","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","article_processing_charge":"No","ec_funded":1,"publisher":"American Association for the Advancement of Science","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"EdHa"}],"pmid":1,"doi":"10.1126/sciadv.add2488","quality_controlled":"1","publication_identifier":{"issn":["2375-2548"]},"isi":1,"issue":"37","language":[{"iso":"eng"}],"project":[{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}],"volume":8,"date_created":"2023-01-16T09:57:10Z","file_date_updated":"2023-01-30T09:27:49Z","type":"journal_article","month":"09","oa_version":"Published Version","abstract":[{"text":"The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.","lang":"eng"}],"date_updated":"2023-08-04T09:49:59Z","_id":"12253","acknowledgement":"We thank K. Aumayer and the team of the biooptics facility at the Vienna Biocenter, particularly P. Pasierbek and T. Müller, for support with microscopy; K. Panser, C. Pribitzer, and the animal facility personnel for taking care of zebrafish; M. Binner and A. Bandura for help with genotyping; M. Codina Tobias for help with establishing the conditions for the Toddler overexpression compensation experiment; T. Lubiana Alves for sharing the code for scRNA-Seq analyses; the Heisenberg laboratory, particularly D. Pinheiro, for joint laboratory meetings, discussions on the project, and providing the tg(gsc:CAAX-GFP) fish line; the Raz laboratory for providing the Lifeact-GFP plasmid; A. Andersen, A. Schier, C.-P. Heisenberg, and E. Tanaka for comments on the manuscript; and the entire Pauli laboratory, particularly K. Gert and V. Deneke, for valuable discussions and feedback on the manuscript. Funding: Work in A.P.’s laboratory has been supported by the IMP, which receives institutional funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936), as well as the FWF START program (Y 1031-B28 to A.P.), the Human Frontier Science Program (HFSP) Career Development Award (CDA00066/2015 to A.P.) and Young Investigator Grant (RGY0079/2020 to A.P.), the SFB RNA-Deco (project number F 80 to A.P.), a Whitman Center Fellowship from the Marine Biological Laboratory (to A.P.), and EMBO-YIP funds (to A.P.). This work was supported by the European Union (European Research Council Starting Grant 851288 to E.H.). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission.","year":"2022","ddc":["570"],"date_published":"2022-09-14T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"         8","citation":{"ama":"Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler gradient guides mesodermal cell migration. <i>Science Advances</i>. 2022;8(37). doi:<a href=\"https://doi.org/10.1126/sciadv.add2488\">10.1126/sciadv.add2488</a>","mla":"Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” <i>Science Advances</i>, vol. 8, no. 37, eadd2488, American Association for the Advancement of Science, 2022, doi:<a href=\"https://doi.org/10.1126/sciadv.add2488\">10.1126/sciadv.add2488</a>.","ista":"Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. 2022. A self-generated Toddler gradient guides mesodermal cell migration. Science Advances. 8(37), eadd2488.","apa":"Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., &#38; Pauli, A. (2022). A self-generated Toddler gradient guides mesodermal cell migration. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.add2488\">https://doi.org/10.1126/sciadv.add2488</a>","ieee":"J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated Toddler gradient guides mesodermal cell migration,” <i>Science Advances</i>, vol. 8, no. 37. American Association for the Advancement of Science, 2022.","chicago":"Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/sciadv.add2488\">https://doi.org/10.1126/sciadv.add2488</a>.","short":"J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances 8 (2022)."},"external_id":{"pmid":["36103529"],"isi":["000888875000009"]},"status":"public"},{"publication":"Nature","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","article_type":"original","publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"department":[{"_id":"EdHa"}],"title":"Retrograde movements determine effective stem cell numbers in the intestine","author":[{"first_name":"Maria","last_name":"Azkanaz","full_name":"Azkanaz, Maria"},{"full_name":"Corominas-Murtra, Bernat","id":"43BE2298-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9806-5643","first_name":"Bernat","last_name":"Corominas-Murtra"},{"full_name":"Ellenbroek, Saskia I. J.","last_name":"Ellenbroek","first_name":"Saskia I. J."},{"first_name":"Lotte","last_name":"Bruens","full_name":"Bruens, Lotte"},{"full_name":"Webb, Anna T.","last_name":"Webb","first_name":"Anna T."},{"last_name":"Laskaris","first_name":"Dimitrios","full_name":"Laskaris, Dimitrios"},{"first_name":"Koen C.","last_name":"Oost","full_name":"Oost, Koen C."},{"full_name":"Lafirenze, Simona J. A.","last_name":"Lafirenze","first_name":"Simona J. A."},{"last_name":"Annusver","first_name":"Karl","full_name":"Annusver, Karl"},{"full_name":"Messal, Hendrik A.","first_name":"Hendrik A.","last_name":"Messal"},{"full_name":"Iqbal, Sharif","first_name":"Sharif","last_name":"Iqbal"},{"first_name":"Dustin J.","last_name":"Flanagan","full_name":"Flanagan, Dustin J."},{"last_name":"Huels","first_name":"David J.","full_name":"Huels, David J."},{"full_name":"Rojas-Rodríguez, Felipe","first_name":"Felipe","last_name":"Rojas-Rodríguez"},{"first_name":"Miguel","last_name":"Vizoso","full_name":"Vizoso, Miguel"},{"last_name":"Kasper","first_name":"Maria","full_name":"Kasper, Maria"},{"full_name":"Sansom, Owen J.","last_name":"Sansom","first_name":"Owen J."},{"full_name":"Snippert, Hugo J.","last_name":"Snippert","first_name":"Hugo J."},{"last_name":"Liberali","first_name":"Prisca","full_name":"Liberali, Prisca"},{"full_name":"Simons, Benjamin D.","last_name":"Simons","first_name":"Benjamin D."},{"full_name":"Katajisto, Pekka","first_name":"Pekka","last_name":"Katajisto"},{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"last_name":"van Rheenen","first_name":"Jacco","full_name":"van Rheenen, Jacco"}],"day":"13","isi":1,"keyword":["Multidisciplinary"],"language":[{"iso":"eng"}],"issue":"7919","project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}],"doi":"10.1038/s41586-022-04962-0","quality_controlled":"1","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"_id":"12274","acknowledgement":"We thank the members of the van Rheenen laboratory for reading the manuscript, and the members of the bioimaging, FACS and animal facility of the NKI for experimental support. We acknowledge the staff at the MedH Flow Cytometry core facility, Karolinska Institutet, and LCI facility/Nikon Center of Excellence, Karolinska Institutet. This work was financially supported by the Netherlands Organization of Scientific Research NWO (Veni grant 863.15.011 to S.I.J.E. and Vici grant 09150182110004 to J.v.R.) and the CancerGenomics.nl (Netherlands Organisation for Scientific Research) program (to J.v.R.) the Doctor Josef Steiner Foundation (to J.v.R). B.D.S. acknowledges funding from the Royal Society E.P. Abraham Research Professorship (RP\\R1\\180165) and the Wellcome Trust (098357/Z/12/Z and 219478/Z/19/Z). B.C.-M. acknowledges the support of the field of excellence ‘Complexity of life in basic research and innovation’ of the University of Graz. O.J.S. and their laboratory acknowledge CRUK core funding to the CRUK Beatson Institute (A17196 and A31287) and CRUK core funding to the Sansom laboratory (A21139). P.K. and their laboratory are supported by grants from the Swedish Research Council (2018-03078), Cancerfonden (190634), Academy of Finland Centre of Excellence (266869, 304591 and 320185) and the Jane and Aatos Erkko Foundation. P.L. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 758617). E.H. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 851288).","year":"2022","volume":607,"date_created":"2023-01-16T10:01:29Z","page":"548-554","abstract":[{"lang":"eng","text":"The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated."}],"date_updated":"2023-10-03T11:16:30Z","month":"07","oa_version":"Submitted Version","type":"journal_article","related_material":{"link":[{"url":"https://github.com/JaccovanRheenenLab/Retrograde_movement_Azkanaz_Nature_2022","relation":"software"}]},"intvolume":"       607","citation":{"short":"M. Azkanaz, B. Corominas-Murtra, S.I.J. Ellenbroek, L. Bruens, A.T. Webb, D. Laskaris, K.C. Oost, S.J.A. Lafirenze, K. Annusver, H.A. Messal, S. Iqbal, D.J. Flanagan, D.J. Huels, F. Rojas-Rodríguez, M. Vizoso, M. Kasper, O.J. Sansom, H.J. Snippert, P. Liberali, B.D. Simons, P. Katajisto, E.B. Hannezo, J. van Rheenen, Nature 607 (2022) 548–554.","chicago":"Azkanaz, Maria, Bernat Corominas-Murtra, Saskia I. J. Ellenbroek, Lotte Bruens, Anna T. Webb, Dimitrios Laskaris, Koen C. Oost, et al. “Retrograde Movements Determine Effective Stem Cell Numbers in the Intestine.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-04962-0\">https://doi.org/10.1038/s41586-022-04962-0</a>.","ieee":"M. Azkanaz <i>et al.</i>, “Retrograde movements determine effective stem cell numbers in the intestine,” <i>Nature</i>, vol. 607, no. 7919. Springer Nature, pp. 548–554, 2022.","apa":"Azkanaz, M., Corominas-Murtra, B., Ellenbroek, S. I. J., Bruens, L., Webb, A. T., Laskaris, D., … van Rheenen, J. (2022). Retrograde movements determine effective stem cell numbers in the intestine. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-04962-0\">https://doi.org/10.1038/s41586-022-04962-0</a>","mla":"Azkanaz, Maria, et al. “Retrograde Movements Determine Effective Stem Cell Numbers in the Intestine.” <i>Nature</i>, vol. 607, no. 7919, Springer Nature, 2022, pp. 548–54, doi:<a href=\"https://doi.org/10.1038/s41586-022-04962-0\">10.1038/s41586-022-04962-0</a>.","ista":"Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P, Simons BD, Katajisto P, Hannezo EB, van Rheenen J. 2022. Retrograde movements determine effective stem cell numbers in the intestine. Nature. 607(7919), 548–554.","ama":"Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, et al. Retrograde movements determine effective stem cell numbers in the intestine. <i>Nature</i>. 2022;607(7919):548-554. doi:<a href=\"https://doi.org/10.1038/s41586-022-04962-0\">10.1038/s41586-022-04962-0</a>"},"status":"public","external_id":{"isi":["000824430000004"],"pmid":["35831497"]},"date_published":"2022-07-13T00:00:00Z","main_file_link":[{"url":"https://helda.helsinki.fi/items/94433455-4854-45c0-9de8-7326caea8780","open_access":"1"}],"publication_status":"published","oa":1},{"volume":12,"date_created":"2023-01-16T10:02:06Z","file_date_updated":"2023-01-30T11:07:27Z","oa_version":"Published Version","month":"09","type":"journal_article","date_updated":"2023-08-04T10:25:49Z","abstract":[{"text":"Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.","lang":"eng"}],"_id":"12277","acknowledgement":"We thank Grzegorz Gradziuk, StevenRiedijk, Janni Harju, and M. R. Schnucki for helpful discussions, and Andriy Goychuk for advice on the image segmentation. This project\r\nwas funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project No. 201269156—SFB 1032 (Projects B01 and B12). D. B. B. is supported by the NOMIS Foundation and in part by a DFG fellowship within the Graduate School of Quantitative Biosciences Munich (QBM), as well as by the Joachim Herz Stiftung.","year":"2022","date_published":"2022-09-20T00:00:00Z","ddc":["530","570"],"oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":"        12","citation":{"chicago":"Brückner, David, Matthew Schmitt, Alexandra Fink, Georg Ladurner, Johannes Flommersfeld, Nicolas Arlt, Edouard B Hannezo, Joachim O. Rädler, and Chase P. Broedersz. “Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration.” <i>Physical Review X</i>. American Physical Society, 2022. <a href=\"https://doi.org/10.1103/physrevx.12.031041\">https://doi.org/10.1103/physrevx.12.031041</a>.","ieee":"D. Brückner <i>et al.</i>, “Geometry adaptation of protrusion and polarity dynamics in confined cell migration,” <i>Physical Review X</i>, vol. 12, no. 3. American Physical Society, 2022.","short":"D. Brückner, M. Schmitt, A. Fink, G. Ladurner, J. Flommersfeld, N. Arlt, E.B. Hannezo, J.O. Rädler, C.P. Broedersz, Physical Review X 12 (2022).","ama":"Brückner D, Schmitt M, Fink A, et al. Geometry adaptation of protrusion and polarity dynamics in confined cell migration. <i>Physical Review X</i>. 2022;12(3). doi:<a href=\"https://doi.org/10.1103/physrevx.12.031041\">10.1103/physrevx.12.031041</a>","apa":"Brückner, D., Schmitt, M., Fink, A., Ladurner, G., Flommersfeld, J., Arlt, N., … Broedersz, C. P. (2022). Geometry adaptation of protrusion and polarity dynamics in confined cell migration. <i>Physical Review X</i>. American Physical Society. <a href=\"https://doi.org/10.1103/physrevx.12.031041\">https://doi.org/10.1103/physrevx.12.031041</a>","ista":"Brückner D, Schmitt M, Fink A, Ladurner G, Flommersfeld J, Arlt N, Hannezo EB, Rädler JO, Broedersz CP. 2022. Geometry adaptation of protrusion and polarity dynamics in confined cell migration. Physical Review X. 12(3), 031041.","mla":"Brückner, David, et al. “Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration.” <i>Physical Review X</i>, vol. 12, no. 3, 031041, American Physical Society, 2022, doi:<a href=\"https://doi.org/10.1103/physrevx.12.031041\">10.1103/physrevx.12.031041</a>."},"external_id":{"arxiv":["2106.01014"],"isi":["000861534700001"]},"status":"public","article_number":"031041","arxiv":1,"title":"Geometry adaptation of protrusion and polarity dynamics in confined cell migration","author":[{"first_name":"David","last_name":"Brückner","full_name":"Brückner, David","id":"e1e86031-6537-11eb-953a-f7ab92be508d","orcid":"0000-0001-7205-2975"},{"first_name":"Matthew","last_name":"Schmitt","full_name":"Schmitt, Matthew"},{"full_name":"Fink, Alexandra","last_name":"Fink","first_name":"Alexandra"},{"last_name":"Ladurner","first_name":"Georg","full_name":"Ladurner, Georg"},{"full_name":"Flommersfeld, Johannes","last_name":"Flommersfeld","first_name":"Johannes"},{"full_name":"Arlt, Nicolas","last_name":"Arlt","first_name":"Nicolas"},{"last_name":"Hannezo","first_name":"Edouard B","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Rädler, Joachim O.","last_name":"Rädler","first_name":"Joachim O."},{"last_name":"Broedersz","first_name":"Chase P.","full_name":"Broedersz, Chase P."}],"file":[{"file_id":"12458","date_updated":"2023-01-30T11:07:27Z","checksum":"40a8fbc3663bf07b37cb80020974d40d","date_created":"2023-01-30T11:07:27Z","access_level":"open_access","file_name":"2022_PhysicalReviewX_Brueckner.pdf","success":1,"file_size":4686804,"relation":"main_file","content_type":"application/pdf","creator":"dernst"}],"day":"20","publication":"Physical Review X","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","scopus_import":"1","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"American Physical Society","department":[{"_id":"EdHa"}],"doi":"10.1103/physrevx.12.031041","quality_controlled":"1","publication_identifier":{"issn":["2160-3308"]},"keyword":["General Physics and Astronomy"],"isi":1,"issue":"3","language":[{"iso":"eng"}]},{"external_id":{"isi":["000822975900002"]},"status":"public","intvolume":"        23","citation":{"short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>.","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>"},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2022-07-11T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","year":"2022","_id":"9794","page":"1246-1255","abstract":[{"text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.","lang":"eng"}],"date_updated":"2023-08-02T06:53:07Z","oa_version":"Published Version","month":"07","type":"journal_article","volume":23,"date_created":"2021-08-06T09:09:11Z","file_date_updated":"2022-07-25T07:11:32Z","project":[{"name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"doi":"10.1038/s41590-022-01257-4","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"publication":"Nature Immunology","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","author":[{"first_name":"Frank P","last_name":"Assen","full_name":"Assen, Frank P","orcid":"0000-0003-3470-6119","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Abe, Jun","first_name":"Jun","last_name":"Abe"},{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav","last_name":"Hons","first_name":"Miroslav"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","last_name":"Hauschild","first_name":"Robert"},{"full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","first_name":"Shayan","last_name":"Shamipour"},{"first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter"},{"first_name":"Tommaso","last_name":"Costanzo","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","id":"D93824F4-D9BA-11E9-BB12-F207E6697425"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel","last_name":"Krens","first_name":"Gabriel"},{"first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"first_name":"Burkhard","last_name":"Ludewig","full_name":"Ludewig, Burkhard"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg"},{"full_name":"Weninger, Wolfgang","first_name":"Wolfgang","last_name":"Weninger"},{"last_name":"Hannezo","first_name":"Edouard B","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"full_name":"Luther, Sanjiv A.","last_name":"Luther","first_name":"Sanjiv A."},{"full_name":"Stein, Jens V.","first_name":"Jens V.","last_name":"Stein"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"file":[{"file_size":11475325,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_name":"2022_NatureImmunology_Assen.pdf","success":1,"date_created":"2022-07-25T07:11:32Z","access_level":"open_access","file_id":"11642","date_updated":"2022-07-25T07:11:32Z","checksum":"628e7b49809f22c75b428842efe70c68"}],"day":"11","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes"}]