[{"has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"W01250-B20","name":"Nano-Analytics of Cellular Systems","_id":"265E2996-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"month":"07","language":[{"iso":"eng"}],"keyword":["cell biology","immunology","leukocyte","migration","microfluidics"],"date_published":"2019-07-24T00:00:00Z","type":"dissertation","publication_identifier":{"isbn":["978-3-99078-002-2"],"eissn":["2663-337X"]},"supervisor":[{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"file":[{"date_updated":"2020-10-17T22:30:03Z","file_name":"Kopf_PhD_Thesis.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2019-10-15T05:28:42Z","checksum":"00d100d6468e31e583051e0a006b640c","file_size":74735267,"embargo_to":"open_access","file_id":"6950","creator":"akopf","relation":"source_file","access_level":"closed"},{"creator":"akopf","file_id":"6951","relation":"main_file","access_level":"open_access","file_name":"Kopf_PhD_Thesis1.pdf","content_type":"application/pdf","date_updated":"2020-10-17T22:30:03Z","file_size":52787224,"checksum":"5d1baa899993ae6ca81aebebe1797000","embargo":"2020-10-16","date_created":"2019-10-15T05:28:47Z"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"link":[{"url":"https://ist.ac.at/en/news/feeling-like-a-cell/","relation":"press_release"}],"record":[{"status":"public","id":"6328","relation":"part_of_dissertation"},{"id":"15","relation":"part_of_dissertation","status":"public"},{"id":"6877","relation":"part_of_dissertation","status":"public"}]},"_id":"6891","author":[{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656","last_name":"Kopf","first_name":"Aglaja"}],"publication_status":"published","department":[{"_id":"MiSi"}],"date_created":"2019-09-19T08:19:44Z","article_processing_charge":"No","alternative_title":["ISTA Thesis"],"title":"The implication of cytoskeletal dynamics on leukocyte migration","page":"171","file_date_updated":"2020-10-17T22:30:03Z","publisher":"Institute of Science and Technology Austria","date_updated":"2023-10-18T08:49:17Z","citation":{"ama":"Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>","apa":"Kopf, A. (2019). <i>The implication of cytoskeletal dynamics on leukocyte migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>","chicago":"Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>.","ieee":"A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019.","mla":"Kopf, Aglaja. <i>The Implication of Cytoskeletal Dynamics on Leukocyte Migration</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>.","short":"A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019.","ista":"Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria."},"year":"2019","doi":"10.15479/AT:ISTA:6891","degree_awarded":"PhD","day":"24","abstract":[{"text":"While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n","lang":"eng"}],"ddc":["570"]},{"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:6947","day":"9","abstract":[{"text":"Lymph nodes  are es s ential organs  of the immune  s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular  cells (FRCs) are  the  main  stromal  cells and  form  a sponge-like extracellular matrix network,   called  conduits ,  which  they   thems elves   enwrap   and  contract.  Lymph,  containing  s oluble  antigens ,  arrive in  lymph  nodes  via afferent lymphatic  vessels that  connect  to  the  s ubcaps ular  s inus   and  conduit  network.  According  to  the  current  paradigm,  the  conduit  network   dis tributes   afferent  lymph  through   lymph  nodes   and  thus   provides   acces s   for  immune  cells to lymph-borne  antigens. An  elas tic  caps ule  s urrounds   the  organ  and  confines   the immune  cells and  FRC  network.   Lymph   nodes   are  completely  packed  with  lymphocytes   and  lymphocyte  numbers  directly  dictates  the size  of  the  organ.  Although  lymphocytes   cons tantly  enter  and  leave  the  lymph  node,  its   s ize  remains   remarkedly   s table  under  homeostatic conditions. It is only partly known  how the cellularity and s ize of the lymph node is regulated and  how  the  lymph  node  is able to swell in inflammation.  The role of the FRC network   in  lymph  node   s welling  and  trans fer  of  fluids   are  inves tigated in  this   thes is.  Furthermore,   we  s tudied  what  trafficking  routes   are  us ed  by  cancer  cells   in  lymph  nodes   to  form  distal metastases.We examined the role of a mechanical feedback in regulation of lymph  node swelling. Using parallel plate compression  and UV-las er  cutting  experiments   we  dis s ected  the  mechanical  force dynamics  of the whole lymph  node, and individually for FRCs  and the  caps ule. Physical forces   generated  by  packed  lymphocytes   directly  affect  the  tens ion  on  the  FRC  network  and  capsule,  which  increases  its  resistance  to   swelling.  This  implies  a  feedback  mechanism  between   tis s ue   pres s ure   and   ability   of   lymphocytes    to   enter   the   organ.   Following   inflammation,  the  lymph  node  swells ∼10 fold in two weeks . Yet, what  is  the role  for tens ion on  the  FRC  network   and  caps ule,  and  how  are  lymphocytes   able  to  enter  in  conditions  that resist swelling remain open ques tions . We s how that tens ion on the FRC network is  important to  limit  the  swelling  rate  of  the  organ  so  that  the  FRC  network  can  grow  in  a  coordinated  fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates  and a dis organized FRC network  in the inflamed lymph  node. Growth  of the FRC network  in  turn  is   expected  to  releas e  tens ion  on  thes e  s tructures   and  lowers   the  res is tance  to  swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of  swelling coincides   with  a  thickening  of  the  caps ule,  which  forms   a  thick  res is tant  band  around  the organ and lowers  tens ion on the FRC network  to form a new force equilibrium.The  FRC  and  conduit   network   are  further   believed  to  be  a  privileged  s ite  of  s oluble  information  within  the  lymph  node,  although  many  details   remain  uns olved.  We  s how  by  3D  ultra-recons truction   that  FRCs   and  antigen  pres enting  cells   cover  the  s urface  of  conduit  s ys tem for more  than 99% and we dis cus s  the implications  for s oluble information  exchangeat the conduit level.Finally, there  is an ongoing debate in the cancer field whether and how cancer cells  in lymph nodes   s eed  dis tal  metas tas es .  We  s how  that  cancer  cells   infus ed  into  the  lymph  node  can  utilize trafficking routes of immune  cells and  rapidly  migrate  to  blood  vessels. Once  in  the  blood circulation,  these cells are able to form  metastases in distal tissues.","lang":"eng"}],"date_updated":"2023-09-13T08:50:57Z","year":"2019","citation":{"short":"F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019.","mla":"Assen, Frank P. <i>Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>.","ista":"Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.","ama":"Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>","apa":"Assen, F. P. (2019). <i>Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>","ieee":"F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.","chicago":"Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>."},"ddc":["570"],"publication_status":"published","article_processing_charge":"No","department":[{"_id":"MiSi"}],"date_created":"2019-10-14T16:54:52Z","alternative_title":["ISTA Thesis"],"title":"Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking","_id":"6947","author":[{"full_name":"Assen, Frank P","orcid":"0000-0003-3470-6119","last_name":"Assen","first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","page":"142","file_date_updated":"2020-11-07T23:30:03Z","publication_identifier":{"issn":["2663-337X"]},"supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"oa":1,"date_published":"2019-10-09T00:00:00Z","type":"dissertation","file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"PhDthesis_FrankAssen_revised2.docx","date_updated":"2020-11-07T23:30:03Z","file_size":214172667,"checksum":"53a739752a500f84d0f8ec953cbbd0b6","embargo_to":"open_access","date_created":"2019-11-06T12:30:02Z","creator":"fassen","file_id":"6990","access_level":"closed","relation":"source_file"},{"creator":"fassen","file_id":"6991","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_name":"PhDthesis_FrankAssen_revised2.pdf","date_updated":"2020-11-07T23:30:03Z","file_size":83637532,"checksum":"8c156b65d9347bb599623a4b09f15d15","embargo":"2020-11-06","date_created":"2019-11-06T12:30:57Z"}],"status":"public","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"664"},{"id":"402","relation":"part_of_dissertation","status":"public"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"oa_version":"Published Version","month":"10","has_accepted_license":"1","language":[{"iso":"eng"}]},{"publication":"Current Biology","month":"10","oa_version":"None","language":[{"iso":"eng"}],"type":"journal_article","date_published":"2019-10-21T00:00:00Z","publication_identifier":{"eissn":["1879-0445"],"issn":["0960-9822"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","issue":"20","author":[{"full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656","last_name":"Kopf","first_name":"Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","pmid":1,"_id":"6979","intvolume":"        29","title":"Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal","date_created":"2019-11-04T15:18:29Z","article_processing_charge":"No","department":[{"_id":"MiSi"}],"publication_status":"published","quality_controlled":"1","page":"R1091-R1093","article_type":"original","publisher":"Cell Press","external_id":{"pmid":["31639357"],"isi":["000491286200016"]},"isi":1,"citation":{"ista":"Kopf A, Sixt MK. 2019. Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. 29(20), R1091–R1093.","mla":"Kopf, Aglaja, and Michael K. Sixt. “Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.” <i>Current Biology</i>, vol. 29, no. 20, Cell Press, 2019, pp. R1091–93, doi:<a href=\"https://doi.org/10.1016/j.cub.2019.08.068\">10.1016/j.cub.2019.08.068</a>.","short":"A. Kopf, M.K. Sixt, Current Biology 29 (2019) R1091–R1093.","ieee":"A. Kopf and M. K. Sixt, “Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal,” <i>Current Biology</i>, vol. 29, no. 20. Cell Press, pp. R1091–R1093, 2019.","chicago":"Kopf, Aglaja, and Michael K Sixt. “Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.” <i>Current Biology</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cub.2019.08.068\">https://doi.org/10.1016/j.cub.2019.08.068</a>.","apa":"Kopf, A., &#38; Sixt, M. K. (2019). Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2019.08.068\">https://doi.org/10.1016/j.cub.2019.08.068</a>","ama":"Kopf A, Sixt MK. Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. <i>Current Biology</i>. 2019;29(20):R1091-R1093. doi:<a href=\"https://doi.org/10.1016/j.cub.2019.08.068\">10.1016/j.cub.2019.08.068</a>"},"year":"2019","date_updated":"2023-09-05T12:43:43Z","day":"21","doi":"10.1016/j.cub.2019.08.068","volume":29},{"page":"922-938","ec_funded":1,"quality_controlled":"1","publisher":"Cell Press","article_type":"review","pmid":1,"_id":"6988","scopus_import":"1","author":[{"full_name":"Nicolai, Leo","last_name":"Nicolai","first_name":"Leo"},{"id":"397A88EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6120-3723","full_name":"Gärtner, Florian R","first_name":"Florian R","last_name":"Gärtner"},{"full_name":"Massberg, Steffen","first_name":"Steffen","last_name":"Massberg"}],"issue":"10","publication_status":"published","article_processing_charge":"No","department":[{"_id":"MiSi"}],"date_created":"2019-11-04T16:27:36Z","title":"Platelets in host defense: Experimental and clinical insights","intvolume":"        40","volume":40,"date_updated":"2023-08-30T07:19:23Z","year":"2019","citation":{"ieee":"L. Nicolai, F. R. Gärtner, and S. Massberg, “Platelets in host defense: Experimental and clinical insights,” <i>Trends in Immunology</i>, vol. 40, no. 10. Cell Press, pp. 922–938, 2019.","chicago":"Nicolai, Leo, Florian R Gärtner, and Steffen Massberg. “Platelets in Host Defense: Experimental and Clinical Insights.” <i>Trends in Immunology</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.it.2019.08.004\">https://doi.org/10.1016/j.it.2019.08.004</a>.","ama":"Nicolai L, Gärtner FR, Massberg S. Platelets in host defense: Experimental and clinical insights. <i>Trends in Immunology</i>. 2019;40(10):922-938. doi:<a href=\"https://doi.org/10.1016/j.it.2019.08.004\">10.1016/j.it.2019.08.004</a>","apa":"Nicolai, L., Gärtner, F. R., &#38; Massberg, S. (2019). Platelets in host defense: Experimental and clinical insights. <i>Trends in Immunology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.it.2019.08.004\">https://doi.org/10.1016/j.it.2019.08.004</a>","ista":"Nicolai L, Gärtner FR, Massberg S. 2019. Platelets in host defense: Experimental and clinical insights. Trends in Immunology. 40(10), 922–938.","mla":"Nicolai, Leo, et al. “Platelets in Host Defense: Experimental and Clinical Insights.” <i>Trends in Immunology</i>, vol. 40, no. 10, Cell Press, 2019, pp. 922–38, doi:<a href=\"https://doi.org/10.1016/j.it.2019.08.004\">10.1016/j.it.2019.08.004</a>.","short":"L. Nicolai, F.R. Gärtner, S. Massberg, Trends in Immunology 40 (2019) 922–938."},"isi":1,"external_id":{"isi":["000493292100005"],"pmid":["31601520"]},"doi":"10.1016/j.it.2019.08.004","day":"01","abstract":[{"text":"Platelets are central players in thrombosis and hemostasis but are increasingly recognized as key components of the immune system. They shape ensuing immune responses by recruiting leukocytes, and support the development of adaptive immunity. Recent data shed new light on the complex role of platelets in immunity. Here, we summarize experimental and clinical data on the role of platelets in host defense against bacteria. Platelets bind, contain, and kill bacteria directly; however, platelet proinflammatory effector functions and cross-talk with the coagulation system, can also result in damage to the host (e.g., acute lung injury and sepsis). Novel clinical insights support this dichotomy: platelet inhibition/thrombocytopenia can be either harmful or protective, depending on pathophysiological context. Clinical studies are currently addressing this aspect in greater depth.","lang":"eng"}],"language":[{"iso":"eng"}],"publication":"Trends in Immunology","oa_version":"None","project":[{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"}],"month":"10","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","date_published":"2019-10-01T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["1471-4906"]}},{"volume":20,"date_updated":"2023-08-30T07:22:20Z","citation":{"short":"K. Yamada, M.K. Sixt, Nature Reviews Molecular Cell Biology 20 (2019) 738–752.","mla":"Yamada, KM, and Michael K. Sixt. “Mechanisms of 3D Cell Migration.” <i>Nature Reviews Molecular Cell Biology</i>, vol. 20, no. 12, Springer Nature, 2019, pp. 738–752, doi:<a href=\"https://doi.org/10.1038/s41580-019-0172-9\">10.1038/s41580-019-0172-9</a>.","ista":"Yamada K, Sixt MK. 2019. Mechanisms of 3D cell migration. Nature Reviews Molecular Cell Biology. 20(12), 738–752.","ama":"Yamada K, Sixt MK. Mechanisms of 3D cell migration. <i>Nature Reviews Molecular Cell Biology</i>. 2019;20(12):738–752. doi:<a href=\"https://doi.org/10.1038/s41580-019-0172-9\">10.1038/s41580-019-0172-9</a>","apa":"Yamada, K., &#38; Sixt, M. K. (2019). Mechanisms of 3D cell migration. <i>Nature Reviews Molecular Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41580-019-0172-9\">https://doi.org/10.1038/s41580-019-0172-9</a>","ieee":"K. Yamada and M. K. Sixt, “Mechanisms of 3D cell migration,” <i>Nature Reviews Molecular Cell Biology</i>, vol. 20, no. 12. Springer Nature, pp. 738–752, 2019.","chicago":"Yamada, KM, and Michael K Sixt. “Mechanisms of 3D Cell Migration.” <i>Nature Reviews Molecular Cell Biology</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41580-019-0172-9\">https://doi.org/10.1038/s41580-019-0172-9</a>."},"year":"2019","isi":1,"external_id":{"pmid":["31582855"],"isi":["000497966900007"]},"doi":"10.1038/s41580-019-0172-9","day":"01","abstract":[{"lang":"eng","text":"Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non- muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration."}],"page":"738–752","quality_controlled":"1","publisher":"Springer Nature","article_type":"review","pmid":1,"_id":"7009","scopus_import":"1","author":[{"first_name":"KM","last_name":"Yamada","full_name":"Yamada, KM"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"issue":"12","publication_status":"published","date_created":"2019-11-12T14:54:42Z","department":[{"_id":"MiSi"}],"article_processing_charge":"No","title":"Mechanisms of 3D cell migration","intvolume":"        20","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_published":"2019-12-01T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["1471-0072"],"eissn":["1471-0080"]},"language":[{"iso":"eng"}],"publication":"Nature Reviews Molecular Cell Biology","oa_version":"None","month":"12"},{"volume":21,"day":"01","doi":"10.1038/s41556-019-0411-5","abstract":[{"lang":"eng","text":"Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence."}],"year":"2019","citation":{"apa":"Yolland, L., Burki, M., Marcotti, S., Luchici, A., Kenny, F. N., Davis, J. R., … Stramer, B. M. (2019). Persistent and polarized global actin flow is essential for directionality during cell migration. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-019-0411-5\">https://doi.org/10.1038/s41556-019-0411-5</a>","ama":"Yolland L, Burki M, Marcotti S, et al. Persistent and polarized global actin flow is essential for directionality during cell migration. <i>Nature Cell Biology</i>. 2019;21(11):1370-1381. doi:<a href=\"https://doi.org/10.1038/s41556-019-0411-5\">10.1038/s41556-019-0411-5</a>","chicago":"Yolland, Lawrence, Mubarik Burki, Stefania Marcotti, Andrei Luchici, Fiona N. Kenny, John Robert Davis, Eduardo Serna-Morales, et al. “Persistent and Polarized Global Actin Flow Is Essential for Directionality during Cell Migration.” <i>Nature Cell Biology</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41556-019-0411-5\">https://doi.org/10.1038/s41556-019-0411-5</a>.","ieee":"L. Yolland <i>et al.</i>, “Persistent and polarized global actin flow is essential for directionality during cell migration,” <i>Nature Cell Biology</i>, vol. 21, no. 11. Springer Nature, pp. 1370–1381, 2019.","short":"L. Yolland, M. Burki, S. Marcotti, A. Luchici, F.N. Kenny, J.R. Davis, E. Serna-Morales, J. Müller, M.K. Sixt, A. Davidson, W. Wood, L.J. Schumacher, R.G. Endres, M. Miodownik, B.M. Stramer, Nature Cell Biology 21 (2019) 1370–1381.","mla":"Yolland, Lawrence, et al. “Persistent and Polarized Global Actin Flow Is Essential for Directionality during Cell Migration.” <i>Nature Cell Biology</i>, vol. 21, no. 11, Springer Nature, 2019, pp. 1370–81, doi:<a href=\"https://doi.org/10.1038/s41556-019-0411-5\">10.1038/s41556-019-0411-5</a>.","ista":"Yolland L, Burki M, Marcotti S, Luchici A, Kenny FN, Davis JR, Serna-Morales E, Müller J, Sixt MK, Davidson A, Wood W, Schumacher LJ, Endres RG, Miodownik M, Stramer BM. 2019. Persistent and polarized global actin flow is essential for directionality during cell migration. Nature Cell Biology. 21(11), 1370–1381."},"date_updated":"2023-09-06T11:08:52Z","external_id":{"pmid":["31685997"],"isi":["000495888300009"]},"isi":1,"publisher":"Springer Nature","article_type":"original","quality_controlled":"1","page":"1370-1381","department":[{"_id":"MiSi"}],"article_processing_charge":"No","date_created":"2019-11-25T08:55:00Z","publication_status":"published","intvolume":"        21","title":"Persistent and polarized global actin flow is essential for directionality during cell migration","scopus_import":"1","_id":"7105","pmid":1,"issue":"11","author":[{"full_name":"Yolland, Lawrence","first_name":"Lawrence","last_name":"Yolland"},{"full_name":"Burki, Mubarik","last_name":"Burki","first_name":"Mubarik"},{"last_name":"Marcotti","first_name":"Stefania","full_name":"Marcotti, Stefania"},{"first_name":"Andrei","last_name":"Luchici","full_name":"Luchici, Andrei"},{"first_name":"Fiona N.","last_name":"Kenny","full_name":"Kenny, Fiona N."},{"last_name":"Davis","first_name":"John Robert","full_name":"Davis, John Robert"},{"first_name":"Eduardo","last_name":"Serna-Morales","full_name":"Serna-Morales, Eduardo"},{"full_name":"Müller, Jan","last_name":"Müller","first_name":"Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K"},{"first_name":"Andrew","last_name":"Davidson","full_name":"Davidson, Andrew"},{"first_name":"Will","last_name":"Wood","full_name":"Wood, Will"},{"first_name":"Linus J.","last_name":"Schumacher","full_name":"Schumacher, Linus J."},{"full_name":"Endres, Robert G.","last_name":"Endres","first_name":"Robert G."},{"full_name":"Miodownik, Mark","last_name":"Miodownik","first_name":"Mark"},{"last_name":"Stramer","first_name":"Brian M.","full_name":"Stramer, Brian M."}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025891","open_access":"1"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication_identifier":{"issn":["1465-7392"],"eissn":["1476-4679"]},"oa":1,"type":"journal_article","date_published":"2019-11-01T00:00:00Z","language":[{"iso":"eng"}],"oa_version":"Submitted Version","month":"11","publication":"Nature Cell Biology"},{"year":"2019","citation":{"apa":"Stürner, T., Tatarnikova, A., Müller, J., Schaffran, B., Cuntz, H., Zhang, Y., … Tavosanis, G. (2019). Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.171397\">https://doi.org/10.1242/dev.171397</a>","ama":"Stürner T, Tatarnikova A, Müller J, et al. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. <i>Development</i>. 2019;146(7). doi:<a href=\"https://doi.org/10.1242/dev.171397\">10.1242/dev.171397</a>","ieee":"T. Stürner <i>et al.</i>, “Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo,” <i>Development</i>, vol. 146, no. 7. The Company of Biologists, 2019.","chicago":"Stürner, Tomke, Anastasia Tatarnikova, Jan Müller, Barbara Schaffran, Hermann Cuntz, Yun Zhang, Maria Nemethova, Sven Bogdan, Vic Small, and Gaia Tavosanis. “Transient Localization of the Arp2/3 Complex Initiates Neuronal Dendrite Branching in Vivo.” <i>Development</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/dev.171397\">https://doi.org/10.1242/dev.171397</a>.","short":"T. Stürner, A. Tatarnikova, J. Müller, B. Schaffran, H. Cuntz, Y. Zhang, M. Nemethova, S. Bogdan, V. Small, G. Tavosanis, Development 146 (2019).","mla":"Stürner, Tomke, et al. “Transient Localization of the Arp2/3 Complex Initiates Neuronal Dendrite Branching in Vivo.” <i>Development</i>, vol. 146, no. 7, dev171397, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/dev.171397\">10.1242/dev.171397</a>.","ista":"Stürner T, Tatarnikova A, Müller J, Schaffran B, Cuntz H, Zhang Y, Nemethova M, Bogdan S, Small V, Tavosanis G. 2019. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. Development. 146(7), dev171397."},"date_updated":"2023-09-07T14:47:00Z","external_id":{"pmid":["30910826"],"isi":["000464583200006"]},"isi":1,"day":"04","doi":"10.1242/dev.171397","abstract":[{"text":"The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.","lang":"eng"}],"volume":146,"scopus_import":"1","pmid":1,"_id":"7404","issue":"7","author":[{"last_name":"Stürner","first_name":"Tomke","full_name":"Stürner, Tomke"},{"first_name":"Anastasia","last_name":"Tatarnikova","full_name":"Tatarnikova, Anastasia"},{"id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D","first_name":"Jan","last_name":"Müller","full_name":"Müller, Jan"},{"last_name":"Schaffran","first_name":"Barbara","full_name":"Schaffran, Barbara"},{"full_name":"Cuntz, Hermann","first_name":"Hermann","last_name":"Cuntz"},{"first_name":"Yun","last_name":"Zhang","full_name":"Zhang, Yun"},{"id":"34E27F1C-F248-11E8-B48F-1D18A9856A87","first_name":"Maria","last_name":"Nemethova","full_name":"Nemethova, Maria"},{"last_name":"Bogdan","first_name":"Sven","full_name":"Bogdan, Sven"},{"full_name":"Small, Vic","first_name":"Vic","last_name":"Small"},{"first_name":"Gaia","last_name":"Tavosanis","full_name":"Tavosanis, Gaia"}],"article_processing_charge":"No","department":[{"_id":"MiSi"}],"date_created":"2020-01-29T16:27:10Z","publication_status":"published","intvolume":"       146","title":"Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo","quality_controlled":"1","publisher":"The Company of Biologists","article_type":"original","type":"journal_article","date_published":"2019-04-04T00:00:00Z","publication_identifier":{"eissn":["1477-9129"],"issn":["0950-1991"]},"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1242/dev.171397"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication":"Development","oa_version":"Published Version","article_number":"dev171397","month":"04","language":[{"iso":"eng"}]},{"publisher":"The Company of Biologists","article_type":"original","quality_controlled":"1","department":[{"_id":"MiSi"}],"date_created":"2020-01-30T10:31:42Z","article_processing_charge":"No","publication_status":"published","intvolume":"       132","title":"GGA2 and RAB13 promote activity-dependent β1-integrin recycling","pmid":1,"_id":"7420","issue":"11","author":[{"last_name":"Sahgal","first_name":"Pranshu","full_name":"Sahgal, Pranshu"},{"first_name":"Jonna H","last_name":"Alanko","orcid":"0000-0002-7698-3061","full_name":"Alanko, Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Icha, Jaroslav","last_name":"Icha","first_name":"Jaroslav"},{"full_name":"Paatero, Ilkka","last_name":"Paatero","first_name":"Ilkka"},{"first_name":"Hellyeh","last_name":"Hamidi","full_name":"Hamidi, Hellyeh"},{"first_name":"Antti","last_name":"Arjonen","full_name":"Arjonen, Antti"},{"first_name":"Mika","last_name":"Pietilä","full_name":"Pietilä, Mika"},{"first_name":"Anne","last_name":"Rokka","full_name":"Rokka, Anne"},{"first_name":"Johanna","last_name":"Ivaska","full_name":"Ivaska, Johanna"}],"volume":132,"day":"07","doi":"10.1242/jcs.233387","abstract":[{"lang":"eng","text":"β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic."}],"year":"2019","citation":{"apa":"Sahgal, P., Alanko, J. H., Icha, J., Paatero, I., Hamidi, H., Arjonen, A., … Ivaska, J. (2019). GGA2 and RAB13 promote activity-dependent β1-integrin recycling. <i>Journal of Cell Science</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/jcs.233387\">https://doi.org/10.1242/jcs.233387</a>","ama":"Sahgal P, Alanko JH, Icha J, et al. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. <i>Journal of Cell Science</i>. 2019;132(11). doi:<a href=\"https://doi.org/10.1242/jcs.233387\">10.1242/jcs.233387</a>","chicago":"Sahgal, Pranshu, Jonna H Alanko, Jaroslav Icha, Ilkka Paatero, Hellyeh Hamidi, Antti Arjonen, Mika Pietilä, Anne Rokka, and Johanna Ivaska. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” <i>Journal of Cell Science</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/jcs.233387\">https://doi.org/10.1242/jcs.233387</a>.","ieee":"P. Sahgal <i>et al.</i>, “GGA2 and RAB13 promote activity-dependent β1-integrin recycling,” <i>Journal of Cell Science</i>, vol. 132, no. 11. The Company of Biologists, 2019.","short":"P. Sahgal, J.H. Alanko, J. Icha, I. Paatero, H. Hamidi, A. Arjonen, M. Pietilä, A. Rokka, J. Ivaska, Journal of Cell Science 132 (2019).","mla":"Sahgal, Pranshu, et al. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” <i>Journal of Cell Science</i>, vol. 132, no. 11, jcs233387, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/jcs.233387\">10.1242/jcs.233387</a>.","ista":"Sahgal P, Alanko JH, Icha J, Paatero I, Hamidi H, Arjonen A, Pietilä M, Rokka A, Ivaska J. 2019. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. 132(11), jcs233387."},"date_updated":"2023-09-06T15:01:00Z","external_id":{"pmid":["31076515"],"isi":["000473327900017"]},"isi":1,"language":[{"iso":"eng"}],"oa_version":"Published Version","article_number":"jcs233387","month":"06","publication":"Journal of Cell Science","main_file_link":[{"url":"https://doi.org/10.1242/jcs.233387","open_access":"1"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"oa":1,"type":"journal_article","date_published":"2019-06-07T00:00:00Z"},{"author":[{"first_name":"Jörg","last_name":"Renkawitz","orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja","first_name":"Aglaja","last_name":"Kopf","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Stopp, Julian A","first_name":"Julian A","last_name":"Stopp","id":"489E3F00-F248-11E8-B48F-1D18A9856A87"},{"last_name":"de Vries","first_name":"Ingrid","full_name":"de Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Meghan K.","last_name":"Driscoll","full_name":"Driscoll, Meghan K."},{"last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Welf","first_name":"Erik S.","full_name":"Welf, Erik S."},{"first_name":"Gaudenz","last_name":"Danuser","full_name":"Danuser, Gaudenz"},{"full_name":"Fiolka, Reto","first_name":"Reto","last_name":"Fiolka"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K"}],"pmid":1,"_id":"6328","scopus_import":"1","title":"Nuclear positioning facilitates amoeboid migration along the path of least resistance","intvolume":"       568","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"date_created":"2019-04-17T06:52:28Z","article_processing_charge":"No","page":"546-550","quality_controlled":"1","ec_funded":1,"article_type":"letter_note","publisher":"Springer Nature","isi":1,"external_id":{"pmid":["30944468"],"isi":["000465594200050"]},"date_updated":"2024-03-25T23:30:22Z","year":"2019","citation":{"chicago":"Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” <i>Nature</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41586-019-1087-5\">https://doi.org/10.1038/s41586-019-1087-5</a>.","ieee":"J. Renkawitz <i>et al.</i>, “Nuclear positioning facilitates amoeboid migration along the path of least resistance,” <i>Nature</i>, vol. 568. Springer Nature, pp. 546–550, 2019.","ama":"Renkawitz J, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. <i>Nature</i>. 2019;568:546-550. doi:<a href=\"https://doi.org/10.1038/s41586-019-1087-5\">10.1038/s41586-019-1087-5</a>","apa":"Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin, J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along the path of least resistance. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-019-1087-5\">https://doi.org/10.1038/s41586-019-1087-5</a>","ista":"Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 568, 546–550.","mla":"Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” <i>Nature</i>, vol. 568, Springer Nature, 2019, pp. 546–50, doi:<a href=\"https://doi.org/10.1038/s41586-019-1087-5\">10.1038/s41586-019-1087-5</a>.","short":"J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin, R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550."},"abstract":[{"lang":"eng","text":"During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion."}],"doi":"10.1038/s41586-019-1087-5","day":"25","volume":568,"publication":"Nature","month":"04","oa_version":"Submitted Version","acknowledged_ssus":[{"_id":"SSU"}],"project":[{"grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373","name":"Cellular navigation along spatial gradients"},{"call_identifier":"FWF","_id":"265FAEBA-B435-11E9-9278-68D0E5697425","name":"Nano-Analytics of Cellular Systems","grant_number":"W01250-B20"},{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014","name":"Molecular and system level view of immune cell migration"}],"language":[{"iso":"eng"}],"date_published":"2019-04-25T00:00:00Z","type":"journal_article","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"link":[{"url":"https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/","description":"News on IST Homepage","relation":"press_release"}],"record":[{"relation":"dissertation_contains","id":"14697","status":"public"},{"id":"6891","relation":"dissertation_contains","status":"public"}]},"status":"public","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/"}]},{"acknowledgement":"M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universität Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT).","volume":217,"ddc":["570"],"doi":"10.1083/jcb.201612051","day":"12","abstract":[{"text":"Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified &gt; 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.","lang":"eng"}],"date_updated":"2023-09-13T08:51:29Z","citation":{"ista":"Brown M, Johnson L, Leone D, Májek P, Vaahtomeri K, Senfter D, Bukosza N, Schachner H, Asfour G, Langer B, Hauschild R, Parapatics K, Hong Y, Bennett K, Kain R, Detmar M, Sixt MK, Jackson D, Kerjaschki D. 2018. Lymphatic exosomes promote dendritic cell migration along guidance cues. Journal of Cell Biology. 217(6), 2205–2221.","mla":"Brown, Markus, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>, vol. 217, no. 6, Rockefeller University Press, 2018, pp. 2205–21, doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>.","short":"M. Brown, L. Johnson, D. Leone, P. Májek, K. Vaahtomeri, D. Senfter, N. Bukosza, H. Schachner, G. Asfour, B. Langer, R. Hauschild, K. Parapatics, Y. Hong, K. Bennett, R. Kain, M. Detmar, M.K. Sixt, D. Jackson, D. Kerjaschki, Journal of Cell Biology 217 (2018) 2205–2221.","ieee":"M. Brown <i>et al.</i>, “Lymphatic exosomes promote dendritic cell migration along guidance cues,” <i>Journal of Cell Biology</i>, vol. 217, no. 6. Rockefeller University Press, pp. 2205–2221, 2018.","chicago":"Brown, Markus, Louise Johnson, Dario Leone, Peter Májek, Kari Vaahtomeri, Daniel Senfter, Nora Bukosza, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>.","apa":"Brown, M., Johnson, L., Leone, D., Májek, P., Vaahtomeri, K., Senfter, D., … Kerjaschki, D. (2018). Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>","ama":"Brown M, Johnson L, Leone D, et al. Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. 2018;217(6):2205-2221. doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>"},"year":"2018","isi":1,"external_id":{"pmid":["29650776"],"isi":["000438077800026"]},"publisher":"Rockefeller University Press","page":"2205 - 2221","ec_funded":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:45:45Z","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"}],"date_created":"2018-12-11T11:45:33Z","article_processing_charge":"No","title":"Lymphatic exosomes promote dendritic cell migration along guidance cues","intvolume":"       217","pmid":1,"_id":"275","scopus_import":"1","author":[{"full_name":"Brown, Markus","first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Johnson","first_name":"Louise","full_name":"Johnson, Louise"},{"last_name":"Leone","first_name":"Dario","full_name":"Leone, Dario"},{"full_name":"Májek, Peter","first_name":"Peter","last_name":"Májek"},{"first_name":"Kari","last_name":"Vaahtomeri","orcid":"0000-0001-7829-3518","full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Senfter","first_name":"Daniel","full_name":"Senfter, Daniel"},{"full_name":"Bukosza, Nora","last_name":"Bukosza","first_name":"Nora"},{"full_name":"Schachner, Helga","last_name":"Schachner","first_name":"Helga"},{"first_name":"Gabriele","last_name":"Asfour","full_name":"Asfour, Gabriele"},{"full_name":"Langer, Brigitte","last_name":"Langer","first_name":"Brigitte"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild"},{"full_name":"Parapatics, Katja","last_name":"Parapatics","first_name":"Katja"},{"full_name":"Hong, Young","last_name":"Hong","first_name":"Young"},{"full_name":"Bennett, Keiryn","first_name":"Keiryn","last_name":"Bennett"},{"full_name":"Kain, Renate","last_name":"Kain","first_name":"Renate"},{"full_name":"Detmar, Michael","last_name":"Detmar","first_name":"Michael"},{"first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"David","last_name":"Jackson","full_name":"Jackson, David"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"}],"issue":"6","file":[{"file_size":2252043,"checksum":"9c7eba51a35c62da8c13f98120b64df4","date_created":"2018-12-17T12:50:07Z","file_name":"2018_JournalCellBiology_Brown.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:45:45Z","relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"5704"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"publist_id":"7627","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2018-04-12T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"oa_version":"Published Version","project":[{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"month":"04","publication":"Journal of Cell Biology","has_accepted_license":"1"},{"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"PLoS One","oa_version":"Published Version","article_number":"e0198330","month":"06","file":[{"access_level":"open_access","relation":"main_file","file_id":"5709","creator":"dernst","date_created":"2018-12-17T14:10:32Z","checksum":"95fc5dc3938b3ad3b7697d10c83cc143","file_size":7682167,"date_updated":"2020-07-14T12:45:45Z","file_name":"2018_Plos_Frick.pdf","content_type":"application/pdf"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2018-06-07T00:00:00Z","publist_id":"7626","oa":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:45:45Z","publisher":"Public Library of Science","article_type":"original","scopus_import":"1","_id":"276","issue":"6","author":[{"full_name":"Frick, Corina","first_name":"Corina","last_name":"Frick"},{"full_name":"Dettinger, Philip","last_name":"Dettinger","first_name":"Philip"},{"first_name":"Jörg","last_name":"Renkawitz","orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jauch, Annaïse","last_name":"Jauch","first_name":"Annaïse"},{"full_name":"Berger, Christoph","last_name":"Berger","first_name":"Christoph"},{"first_name":"Mike","last_name":"Recher","full_name":"Recher, Mike"},{"full_name":"Schroeder, Timm","first_name":"Timm","last_name":"Schroeder"},{"full_name":"Mehling, Matthias","first_name":"Matthias","last_name":"Mehling"}],"department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:45:34Z","article_processing_charge":"No","publication_status":"published","intvolume":"        13","title":"Nano-scale microfluidics to study 3D chemotaxis at the single cell level","volume":13,"acknowledgement":"This work was supported by the Swiss National Science Foundation (MD-PhD fellowships, 323530_164221 to C.F.; and 323630_151483 to A.J.; grant PZ00P3_144863 to M.R, grant 31003A_156431 to T.S.; PZ00P3_148000 to C.T.B.; PZ00P3_154733 to M.M.), a Novartis “FreeNovation” grant to M.M. and T.S. and an EMBO long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) to J.R.. M.R. was supported by the Gebert Rüf Foundation (GRS 058/14). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","ddc":["570"],"year":"2018","citation":{"short":"C. Frick, P. Dettinger, J. Renkawitz, A. Jauch, C. Berger, M. Recher, T. Schroeder, M. Mehling, PLoS One 13 (2018).","mla":"Frick, Corina, et al. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” <i>PLoS One</i>, vol. 13, no. 6, e0198330, Public Library of Science, 2018, doi:<a href=\"https://doi.org/10.1371/journal.pone.0198330\">10.1371/journal.pone.0198330</a>.","ista":"Frick C, Dettinger P, Renkawitz J, Jauch A, Berger C, Recher M, Schroeder T, Mehling M. 2018. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 13(6), e0198330.","apa":"Frick, C., Dettinger, P., Renkawitz, J., Jauch, A., Berger, C., Recher, M., … Mehling, M. (2018). Nano-scale microfluidics to study 3D chemotaxis at the single cell level. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0198330\">https://doi.org/10.1371/journal.pone.0198330</a>","ama":"Frick C, Dettinger P, Renkawitz J, et al. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. <i>PLoS One</i>. 2018;13(6). doi:<a href=\"https://doi.org/10.1371/journal.pone.0198330\">10.1371/journal.pone.0198330</a>","chicago":"Frick, Corina, Philip Dettinger, Jörg Renkawitz, Annaïse Jauch, Christoph Berger, Mike Recher, Timm Schroeder, and Matthias Mehling. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” <i>PLoS One</i>. Public Library of Science, 2018. <a href=\"https://doi.org/10.1371/journal.pone.0198330\">https://doi.org/10.1371/journal.pone.0198330</a>.","ieee":"C. Frick <i>et al.</i>, “Nano-scale microfluidics to study 3D chemotaxis at the single cell level,” <i>PLoS One</i>, vol. 13, no. 6. Public Library of Science, 2018."},"date_updated":"2023-09-13T09:00:15Z","external_id":{"isi":["000434384900031"]},"isi":1,"day":"07","doi":"10.1371/journal.pone.0198330","abstract":[{"text":"Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controlla-bility of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo.","lang":"eng"}]},{"volume":45,"external_id":{"pmid":["29738712"],"isi":["000432461400009"]},"isi":1,"year":"2018","citation":{"ieee":"A. Ratheesh <i>et al.</i>, “Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration,” <i>Developmental Cell</i>, vol. 45, no. 3. Elsevier, pp. 331–346, 2018.","chicago":"Ratheesh, Aparna, Julia Bicher, Michael Smutny, Jana Veselá, Ekaterina Papusheva, Gabriel Krens, Walter Kaufmann, Attila György, Alessandra M Casano, and Daria E Siekhaus. “Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.” <i>Developmental Cell</i>. Elsevier, 2018. <a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">https://doi.org/10.1016/j.devcel.2018.04.002</a>.","apa":"Ratheesh, A., Bicher, J., Smutny, M., Veselá, J., Papusheva, E., Krens, G., … Siekhaus, D. E. (2018). Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">https://doi.org/10.1016/j.devcel.2018.04.002</a>","ama":"Ratheesh A, Bicher J, Smutny M, et al. Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. <i>Developmental Cell</i>. 2018;45(3):331-346. doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">10.1016/j.devcel.2018.04.002</a>","ista":"Ratheesh A, Bicher J, Smutny M, Veselá J, Papusheva E, Krens G, Kaufmann W, György A, Casano AM, Siekhaus DE. 2018. Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. Developmental Cell. 45(3), 331–346.","mla":"Ratheesh, Aparna, et al. “Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.” <i>Developmental Cell</i>, vol. 45, no. 3, Elsevier, 2018, pp. 331–46, doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">10.1016/j.devcel.2018.04.002</a>.","short":"A. Ratheesh, J. Bicher, M. Smutny, J. Veselá, E. Papusheva, G. Krens, W. Kaufmann, A. György, A.M. Casano, D.E. Siekhaus, Developmental Cell 45 (2018) 331–346."},"date_updated":"2023-09-11T13:22:13Z","abstract":[{"lang":"eng","text":"Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo."}],"day":"07","doi":"10.1016/j.devcel.2018.04.002","quality_controlled":"1","ec_funded":1,"page":"331 - 346","article_type":"original","publisher":"Elsevier","issue":"3","author":[{"id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7190-0776","full_name":"Ratheesh, Aparna","first_name":"Aparna","last_name":"Ratheesh"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Biebl, Julia","last_name":"Biebl","first_name":"Julia"},{"first_name":"Michael","last_name":"Smutny","full_name":"Smutny, Michael"},{"id":"433253EE-F248-11E8-B48F-1D18A9856A87","full_name":"Veselá, Jana","first_name":"Jana","last_name":"Veselá"},{"id":"41DB591E-F248-11E8-B48F-1D18A9856A87","first_name":"Ekaterina","last_name":"Papusheva","full_name":"Papusheva, Ekaterina"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","last_name":"Krens","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","first_name":"Walter","last_name":"Kaufmann"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","last_name":"György","first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"id":"3DBA3F4E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6009-6804","full_name":"Casano, Alessandra M","first_name":"Alessandra M","last_name":"Casano"},{"last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","pmid":1,"_id":"308","intvolume":"        45","title":"Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration","article_processing_charge":"No","date_created":"2018-12-11T11:45:44Z","department":[{"_id":"DaSi"},{"_id":"CaHe"},{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"MiSi"}],"publication_status":"published","status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"link":[{"url":"https://ist.ac.at/en/news/cells-change-tension-to-make-tissue-barriers-easier-to-get-through/","relation":"press_release","description":"News on IST Homepage"}]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.devcel.2018.04.002"}],"type":"journal_article","date_published":"2018-05-07T00:00:00Z","oa":1,"language":[{"iso":"eng"}],"publication":"Developmental Cell","month":"05","project":[{"grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen","_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"334077","name":"Investigating the role of transporters in invasive migration through junctions","_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"SSU"}]},{"language":[{"iso":"eng"}],"publication":"Developmental Cell","oa_version":"Published Version","month":"02","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/29486189","open_access":"1"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","type":"journal_article","date_published":"2018-02-26T00:00:00Z","publist_id":"7547","oa":1,"quality_controlled":"1","page":"405 - 406","publisher":"Cell Press","scopus_import":"1","_id":"318","pmid":1,"issue":"4","author":[{"id":"3DBA3F4E-F248-11E8-B48F-1D18A9856A87","last_name":"Casano","first_name":"Alessandra M","full_name":"Casano, Alessandra M","orcid":"0000-0002-6009-6804"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"article_processing_charge":"No","date_created":"2018-12-11T11:45:47Z","department":[{"_id":"MiSi"}],"publication_status":"published","intvolume":"        44","title":"A fat lot of good for wound healing","acknowledgement":"Short Survey","volume":44,"citation":{"chicago":"Casano, Alessandra M, and Michael K Sixt. “A Fat Lot of Good for Wound Healing.” <i>Developmental Cell</i>. Cell Press, 2018. <a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">https://doi.org/10.1016/j.devcel.2018.02.009</a>.","ieee":"A. M. Casano and M. K. Sixt, “A fat lot of good for wound healing,” <i>Developmental Cell</i>, vol. 44, no. 4. Cell Press, pp. 405–406, 2018.","ama":"Casano AM, Sixt MK. A fat lot of good for wound healing. <i>Developmental Cell</i>. 2018;44(4):405-406. doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">10.1016/j.devcel.2018.02.009</a>","apa":"Casano, A. M., &#38; Sixt, M. K. (2018). A fat lot of good for wound healing. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">https://doi.org/10.1016/j.devcel.2018.02.009</a>","ista":"Casano AM, Sixt MK. 2018. A fat lot of good for wound healing. Developmental Cell. 44(4), 405–406.","mla":"Casano, Alessandra M., and Michael K. Sixt. “A Fat Lot of Good for Wound Healing.” <i>Developmental Cell</i>, vol. 44, no. 4, Cell Press, 2018, pp. 405–06, doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">10.1016/j.devcel.2018.02.009</a>.","short":"A.M. Casano, M.K. Sixt, Developmental Cell 44 (2018) 405–406."},"year":"2018","date_updated":"2023-09-08T11:42:28Z","external_id":{"pmid":["29486189"],"isi":["000426150700002"]},"isi":1,"day":"26","doi":"10.1016/j.devcel.2018.02.009","abstract":[{"lang":"eng","text":"The insect’s fat body combines metabolic and immunological functions. In this issue of Developmental Cell, Franz et al. (2018) show that in Drosophila, cells of the fat body are not static, but can actively “swim” toward sites of epithelial injury, where they physically clog the wound and locally secrete antimicrobial peptides."}]},{"acknowledgement":"First of all I would like to thank Michael Sixt for giving me the opportunity to work in \r\nhis group and for his support throughout the years. He is a truly inspiring person and \r\nthe  best  boss  one  can  imagine.  I  would  also  like  to  thank  all  current  and  past \r\nmembers of the Sixt group for their help and the great working atmosphere in the lab. \r\nIt is a true privilege to work with such a bright, funny and friendly group of people and \r\nI’m  proud  that  I  could  be  part  of  it.  Furthermore,  I  would  like  to  say  ‘thank  you’  to Daria Siekhaus for all the meetings and discussion we had throughout the years \r\nand to  Federica  Benvenuti  for  being  part  of  my  committee.  I  am  also  grateful  to  Jack \r\nMerrin  in  the  nanofabrication  facility  and  all  the  people  working  in  the  bioimaging-\r\n, the electron microscopy- and the preclinical facilities.","ddc":["571","599","610"],"day":"12","doi":"10.15479/AT:ISTA:th_998","degree_awarded":"PhD","abstract":[{"lang":"eng","text":"In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. "}],"citation":{"apa":"Leithner, A. F. (2018). <i>Branched actin networks in dendritic cell biology</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>","ama":"Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>","ieee":"A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute of Science and Technology Austria, 2018.","chicago":"Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>.","short":"A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute of Science and Technology Austria, 2018.","mla":"Leithner, Alexander F. <i>Branched Actin Networks in Dendritic Cell Biology</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>.","ista":"Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria."},"year":"2018","date_updated":"2023-09-07T12:39:44Z","publisher":"Institute of Science and Technology Austria","page":"99","file_date_updated":"2021-02-11T23:30:17Z","article_processing_charge":"No","department":[{"_id":"MiSi"}],"date_created":"2018-12-11T11:45:49Z","publication_status":"published","pubrep_id":"998","alternative_title":["ISTA Thesis"],"title":"Branched actin networks in dendritic cell biology","_id":"323","author":[{"first_name":"Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"}],"file":[{"date_updated":"2021-02-11T23:30:17Z","file_name":"PhD_thesis_AlexLeithner_final_version.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2019-04-05T09:23:11Z","embargo_to":"open_access","file_size":29027671,"checksum":"d5e3edbac548c26c1fa43a4b37a54a4c","file_id":"6219","creator":"dernst","relation":"source_file","access_level":"closed"},{"file_id":"6220","creator":"dernst","access_level":"open_access","relation":"main_file","date_updated":"2021-02-11T11:17:16Z","content_type":"application/pdf","file_name":"PhD_thesis_AlexLeithner.pdf","embargo":"2019-04-15","date_created":"2019-04-05T09:23:11Z","file_size":66045341,"checksum":"071f7476db29e41146824ebd0697cb10"}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"1321"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication_identifier":{"issn":["2663-337X"]},"oa":1,"publist_id":"7542","supervisor":[{"orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"dissertation","date_published":"2018-04-12T00:00:00Z","language":[{"iso":"eng"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"month":"04","has_accepted_license":"1"},{"external_id":{"isi":["000451920600002"]},"isi":1,"year":"2018","citation":{"ista":"Reversat A, Sixt MK. 2018. IgM’s exit route. Journal of Experimental Medicine. 215(12), 2959–2961.","short":"A. Reversat, M.K. Sixt, Journal of Experimental Medicine 215 (2018) 2959–2961.","mla":"Reversat, Anne, and Michael K. Sixt. “IgM’s Exit Route.” <i>Journal of Experimental Medicine</i>, vol. 215, no. 12, Rockefeller University Press, 2018, pp. 2959–61, doi:<a href=\"https://doi.org/10.1084/jem.20181934\">10.1084/jem.20181934</a>.","ieee":"A. Reversat and M. K. Sixt, “IgM’s exit route,” <i>Journal of Experimental Medicine</i>, vol. 215, no. 12. Rockefeller University Press, pp. 2959–2961, 2018.","chicago":"Reversat, Anne, and Michael K Sixt. “IgM’s Exit Route.” <i>Journal of Experimental Medicine</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1084/jem.20181934\">https://doi.org/10.1084/jem.20181934</a>.","apa":"Reversat, A., &#38; Sixt, M. K. (2018). IgM’s exit route. <i>Journal of Experimental Medicine</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1084/jem.20181934\">https://doi.org/10.1084/jem.20181934</a>","ama":"Reversat A, Sixt MK. IgM’s exit route. <i>Journal of Experimental Medicine</i>. 2018;215(12):2959-2961. doi:<a href=\"https://doi.org/10.1084/jem.20181934\">10.1084/jem.20181934</a>"},"date_updated":"2023-09-11T14:12:06Z","abstract":[{"text":"The release of IgM is the first line of an antibody response and precedes the generation of high affinity IgG in germinal centers. Once secreted by freshly activated plasmablasts, IgM is released into the efferent lymph of reactive lymph nodes as early as 3 d after immunization. As pentameric IgM has an enormous size of 1,000 kD, its diffusibility is low, and one might wonder how it can pass through the densely lymphocyte-packed environment of a lymph node parenchyma in order to reach its exit. In this issue of JEM, Thierry et al. show that, in order to reach the blood stream, IgM molecules take a specific micro-anatomical route via lymph node conduits.","lang":"eng"}],"day":"20","doi":"10.1084/jem.20181934","ddc":["570"],"volume":215,"issue":"12","author":[{"id":"35B76592-F248-11E8-B48F-1D18A9856A87","full_name":"Reversat, Anne","orcid":"0000-0003-0666-8928","last_name":"Reversat","first_name":"Anne"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"scopus_import":"1","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","_id":"5672","intvolume":"       215","title":"IgM's exit route","article_processing_charge":"No","date_created":"2018-12-16T22:59:18Z","department":[{"_id":"MiSi"}],"publication_status":"published","file_date_updated":"2020-07-14T12:47:09Z","quality_controlled":"1","page":"2959-2961","publisher":"Rockefeller University Press","type":"journal_article","date_published":"2018-11-20T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"oa":1,"publication_identifier":{"issn":["00221007"]},"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"access_level":"open_access","relation":"main_file","creator":"dernst","file_id":"5931","file_size":1216437,"checksum":"687beea1d64c213f4cb9e3c29ec11a14","date_created":"2019-02-06T08:49:52Z","content_type":"application/pdf","file_name":"2018_JournalExperMed_Reversat.pdf","date_updated":"2020-07-14T12:47:09Z"}],"has_accepted_license":"1","publication":"Journal of Experimental Medicine","month":"11","oa_version":"Published Version","language":[{"iso":"eng"}]},{"publication_status":"published","article_processing_charge":"No","date_created":"2019-01-20T22:59:18Z","department":[{"_id":"MiSi"}],"title":"Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data","intvolume":"        15","_id":"5858","scopus_import":"1","author":[{"last_name":"Hross","first_name":"Sabrina","full_name":"Hross, Sabrina"},{"last_name":"Theis","first_name":"Fabian J.","full_name":"Theis, Fabian J."},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"},{"last_name":"Hasenauer","first_name":"Jan","full_name":"Hasenauer, Jan"}],"issue":"149","publisher":"Royal Society Publishing","quality_controlled":"1","file_date_updated":"2020-07-14T12:47:13Z","doi":"10.1098/rsif.2018.0600","day":"05","abstract":[{"text":"Spatial patterns are ubiquitous on the subcellular, cellular and tissue level, and can be studied using imaging techniques such as light and fluorescence microscopy. Imaging data provide quantitative information about biological systems; however, mechanisms causing spatial patterning often remain elusive. In recent years, spatio-temporal mathematical modelling has helped to overcome this problem. Yet, outliers and structured noise limit modelling of whole imaging data, and models often consider spatial summary statistics. Here, we introduce an integrated data-driven modelling approach that can cope with measurement artefacts and whole imaging data. Our approach combines mechanistic models of the biological processes with robust statistical models of the measurement process. The parameters of the integrated model are calibrated using a maximum-likelihood approach. We used this integrated modelling approach to study in vivo gradients of the chemokine (C-C motif) ligand 21 (CCL21). CCL21 gradients guide dendritic cells and are important in the adaptive immune response. Using artificial data, we verified that the integrated modelling approach provides reliable parameter estimates in the presence of measurement noise and that bias and variance of these estimates are reduced compared to conventional approaches. The application to experimental data allowed the parametrization and subsequent refinement of the model using additional mechanisms. Among other results, model-based hypothesis testing predicted lymphatic vessel-dependent concentration of heparan sulfate, the binding partner of CCL21. The selected model provided an accurate description of the experimental data and was partially validated using published data. Our findings demonstrate that integrated statistical modelling of whole imaging data is computationally feasible and can provide novel biological insights.","lang":"eng"}],"date_updated":"2023-09-13T08:55:05Z","year":"2018","citation":{"ista":"Hross S, Theis FJ, Sixt MK, Hasenauer J. 2018. Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data. Journal of the Royal Society Interface. 15(149), 20180600.","short":"S. Hross, F.J. Theis, M.K. Sixt, J. Hasenauer, Journal of the Royal Society Interface 15 (2018).","mla":"Hross, Sabrina, et al. “Mechanistic Description of Spatial Processes Using Integrative Modelling of Noise-Corrupted Imaging Data.” <i>Journal of the Royal Society Interface</i>, vol. 15, no. 149, 20180600, Royal Society Publishing, 2018, doi:<a href=\"https://doi.org/10.1098/rsif.2018.0600\">10.1098/rsif.2018.0600</a>.","chicago":"Hross, Sabrina, Fabian J. Theis, Michael K Sixt, and Jan Hasenauer. “Mechanistic Description of Spatial Processes Using Integrative Modelling of Noise-Corrupted Imaging Data.” <i>Journal of the Royal Society Interface</i>. Royal Society Publishing, 2018. <a href=\"https://doi.org/10.1098/rsif.2018.0600\">https://doi.org/10.1098/rsif.2018.0600</a>.","ieee":"S. Hross, F. J. Theis, M. K. Sixt, and J. Hasenauer, “Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data,” <i>Journal of the Royal Society Interface</i>, vol. 15, no. 149. Royal Society Publishing, 2018.","ama":"Hross S, Theis FJ, Sixt MK, Hasenauer J. Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data. <i>Journal of the Royal Society Interface</i>. 2018;15(149). doi:<a href=\"https://doi.org/10.1098/rsif.2018.0600\">10.1098/rsif.2018.0600</a>","apa":"Hross, S., Theis, F. J., Sixt, M. K., &#38; Hasenauer, J. (2018). Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data. <i>Journal of the Royal Society Interface</i>. Royal Society Publishing. <a href=\"https://doi.org/10.1098/rsif.2018.0600\">https://doi.org/10.1098/rsif.2018.0600</a>"},"isi":1,"external_id":{"isi":["000456783800011"]},"volume":15,"ddc":["570"],"oa_version":"Published Version","month":"12","article_number":"20180600","publication":"Journal of the Royal Society Interface","has_accepted_license":"1","language":[{"iso":"eng"}],"publication_identifier":{"issn":["17425689"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2018-12-05T00:00:00Z","type":"journal_article","file":[{"content_type":"application/pdf","file_name":"2018_Interface_Hross.pdf","date_updated":"2020-07-14T12:47:13Z","checksum":"56eb4308a15b7190bff938fab1f780e8","file_size":1464288,"date_created":"2019-02-05T14:46:44Z","creator":"dernst","file_id":"5925","relation":"main_file","access_level":"open_access"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"},{"language":[{"iso":"eng"}],"article_number":"e37888","month":"06","oa_version":"Published Version","has_accepted_license":"1","publication":"eLife","status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"access_level":"open_access","relation":"main_file","file_id":"5973","creator":"dernst","date_created":"2019-02-13T10:52:11Z","checksum":"f1c7ec2a809408d763c4b529a98f9a3b","file_size":358141,"date_updated":"2020-07-14T12:47:13Z","file_name":"2018_eLife_Alanko.pdf","content_type":"application/pdf"}],"oa":1,"publication_identifier":{"issn":["2050084X"]},"type":"journal_article","date_published":"2018-06-06T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_type":"original","publisher":"eLife Sciences Publications","file_date_updated":"2020-07-14T12:47:13Z","quality_controlled":"1","intvolume":"         7","title":"The cell sets the tone","date_created":"2019-01-20T22:59:19Z","department":[{"_id":"MiSi"}],"article_processing_charge":"No","publication_status":"published","author":[{"id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","first_name":"Jonna H","last_name":"Alanko","orcid":"0000-0002-7698-3061","full_name":"Alanko, Jonna H"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"scopus_import":"1","_id":"5861","ddc":["570"],"volume":7,"abstract":[{"lang":"eng","text":"In zebrafish larvae, it is the cell type that determines how the cell responds to a chemokine signal."}],"day":"06","doi":"10.7554/eLife.37888","external_id":{"isi":["000434375000001"]},"isi":1,"citation":{"short":"J.H. Alanko, M.K. Sixt, ELife 7 (2018).","mla":"Alanko, Jonna H., and Michael K. Sixt. “The Cell Sets the Tone.” <i>ELife</i>, vol. 7, e37888, eLife Sciences Publications, 2018, doi:<a href=\"https://doi.org/10.7554/eLife.37888\">10.7554/eLife.37888</a>.","ista":"Alanko JH, Sixt MK. 2018. The cell sets the tone. eLife. 7, e37888.","ama":"Alanko JH, Sixt MK. The cell sets the tone. <i>eLife</i>. 2018;7. doi:<a href=\"https://doi.org/10.7554/eLife.37888\">10.7554/eLife.37888</a>","apa":"Alanko, J. H., &#38; Sixt, M. K. (2018). The cell sets the tone. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.37888\">https://doi.org/10.7554/eLife.37888</a>","ieee":"J. H. Alanko and M. K. Sixt, “The cell sets the tone,” <i>eLife</i>, vol. 7. eLife Sciences Publications, 2018.","chicago":"Alanko, Jonna H, and Michael K Sixt. “The Cell Sets the Tone.” <i>ELife</i>. eLife Sciences Publications, 2018. <a href=\"https://doi.org/10.7554/eLife.37888\">https://doi.org/10.7554/eLife.37888</a>."},"year":"2018","date_updated":"2023-09-19T10:01:39Z"},{"date_updated":"2023-09-19T14:29:32Z","citation":{"apa":"Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-018-04342-1\">https://doi.org/10.1038/s41467-018-04342-1</a>","ama":"Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. <i>Nature Communications</i>. 2018;9(1). doi:<a href=\"https://doi.org/10.1038/s41467-018-04342-1\">10.1038/s41467-018-04342-1</a>","chicago":"Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” <i>Nature Communications</i>. Springer Nature, 2018. <a href=\"https://doi.org/10.1038/s41467-018-04342-1\">https://doi.org/10.1038/s41467-018-04342-1</a>.","ieee":"M. Morri <i>et al.</i>, “Optical functionalization of human class A orphan G-protein-coupled receptors,” <i>Nature Communications</i>, vol. 9, no. 1. Springer Nature, 2018.","short":"M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).","mla":"Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” <i>Nature Communications</i>, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:<a href=\"https://doi.org/10.1038/s41467-018-04342-1\">10.1038/s41467-018-04342-1</a>.","ista":"Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950."},"year":"2018","isi":1,"external_id":{"isi":["000432280000006"]},"doi":"10.1038/s41467-018-04342-1","day":"01","abstract":[{"text":"G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.","lang":"eng"}],"volume":9,"ddc":["570"],"_id":"5984","scopus_import":"1","author":[{"first_name":"Maurizio","last_name":"Morri","full_name":"Morri, Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Inmaculada","last_name":"Sanchez-Romero","full_name":"Sanchez-Romero, Inmaculada","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tichy","first_name":"Alexandra-Madelaine","full_name":"Tichy, Alexandra-Madelaine","id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87"},{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Kainrath","full_name":"Kainrath, Stephanie"},{"first_name":"Elliot J.","last_name":"Gerrard","full_name":"Gerrard, Elliot J."},{"id":"435ACB3A-F248-11E8-B48F-1D18A9856A87","last_name":"Hirschfeld","first_name":"Priscila","full_name":"Hirschfeld, Priscila"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Jan","full_name":"Schwarz, Jan"},{"orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"issue":"1","publication_status":"published","department":[{"_id":"HaJa"},{"_id":"CaGu"},{"_id":"MiSi"}],"date_created":"2019-02-14T10:50:24Z","article_processing_charge":"No","title":"Optical functionalization of human class A orphan G-protein-coupled receptors","intvolume":"         9","quality_controlled":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:47:14Z","publisher":"Springer Nature","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2018-12-01T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["2041-1723"]},"oa":1,"file":[{"relation":"main_file","access_level":"open_access","file_id":"5985","creator":"kschuh","date_created":"2019-02-14T10:58:29Z","file_size":1349914,"checksum":"8325fcc194264af4749e662a73bf66b5","date_updated":"2020-07-14T12:47:14Z","file_name":"2018_Springer_Morri.pdf","content_type":"application/pdf"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication":"Nature Communications","has_accepted_license":"1","oa_version":"Published Version","project":[{"_id":"25548C20-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"303564","name":"Microbial Ion Channels for Synthetic Neurobiology"},{"_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets"}],"month":"12","article_number":"1950","language":[{"iso":"eng"}]},{"file":[{"date_created":"2019-02-14T12:34:29Z","file_size":6668971,"checksum":"e98465b4416b3e804c47f40086932af2","date_updated":"2020-07-14T12:47:15Z","file_name":"2018_ASCB_Dolati.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"5994","creator":"kschuh"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"date_published":"2018-11-01T00:00:00Z","type":"journal_article","publication_identifier":{"eissn":["1939-4586"]},"oa":1,"language":[{"iso":"eng"}],"publication":"Molecular Biology of the Cell","has_accepted_license":"1","oa_version":"Published Version","month":"11","volume":29,"ddc":["570"],"date_updated":"2023-09-19T14:30:23Z","year":"2018","citation":{"apa":"Dolati, S., Kage, F., Mueller, J., Müsken, M., Kirchner, M., Dittmar, G., … Falcke, M. (2018). On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. <i>Molecular Biology of the Cell</i>. American Society for Cell Biology . <a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">https://doi.org/10.1091/mbc.e18-02-0082</a>","ama":"Dolati S, Kage F, Mueller J, et al. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. <i>Molecular Biology of the Cell</i>. 2018;29(22):2674-2686. doi:<a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">10.1091/mbc.e18-02-0082</a>","ieee":"S. Dolati <i>et al.</i>, “On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility,” <i>Molecular Biology of the Cell</i>, vol. 29, no. 22. American Society for Cell Biology , pp. 2674–2686, 2018.","chicago":"Dolati, Setareh, Frieda Kage, Jan Mueller, Mathias Müsken, Marieluise Kirchner, Gunnar Dittmar, Michael K Sixt, Klemens Rottner, and Martin Falcke. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” <i>Molecular Biology of the Cell</i>. American Society for Cell Biology , 2018. <a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">https://doi.org/10.1091/mbc.e18-02-0082</a>.","mla":"Dolati, Setareh, et al. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” <i>Molecular Biology of the Cell</i>, vol. 29, no. 22, American Society for Cell Biology , 2018, pp. 2674–86, doi:<a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">10.1091/mbc.e18-02-0082</a>.","short":"S. Dolati, F. Kage, J. Mueller, M. Müsken, M. Kirchner, G. Dittmar, M.K. Sixt, K. Rottner, M. Falcke, Molecular Biology of the Cell 29 (2018) 2674–2686.","ista":"Dolati S, Kage F, Mueller J, Müsken M, Kirchner M, Dittmar G, Sixt MK, Rottner K, Falcke M. 2018. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. 29(22), 2674–2686."},"isi":1,"external_id":{"isi":["000455641000011"],"pmid":["30156465"]},"doi":"10.1091/mbc.e18-02-0082","day":"01","abstract":[{"text":"Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow.","lang":"eng"}],"page":"2674-2686","quality_controlled":"1","file_date_updated":"2020-07-14T12:47:15Z","publisher":"American Society for Cell Biology ","_id":"5992","pmid":1,"scopus_import":"1","author":[{"last_name":"Dolati","first_name":"Setareh","full_name":"Dolati, Setareh"},{"last_name":"Kage","first_name":"Frieda","full_name":"Kage, Frieda"},{"first_name":"Jan","last_name":"Mueller","full_name":"Mueller, Jan"},{"last_name":"Müsken","first_name":"Mathias","full_name":"Müsken, Mathias"},{"first_name":"Marieluise","last_name":"Kirchner","full_name":"Kirchner, Marieluise"},{"first_name":"Gunnar","last_name":"Dittmar","full_name":"Dittmar, Gunnar"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"},{"full_name":"Rottner, Klemens","first_name":"Klemens","last_name":"Rottner"},{"last_name":"Falcke","first_name":"Martin","full_name":"Falcke, Martin"}],"issue":"22","publication_status":"published","article_processing_charge":"No","date_created":"2019-02-14T12:25:47Z","department":[{"_id":"MiSi"}],"title":"On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility","intvolume":"        29"},{"file":[{"date_updated":"2020-07-14T12:47:28Z","file_name":"2018_BioProtocol_Fan.pdf","content_type":"application/pdf","date_created":"2019-04-30T08:04:33Z","checksum":"d4588377e789da7f360b553ae02c5119","file_size":2928337,"file_id":"6360","creator":"dernst","access_level":"open_access","relation":"main_file"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2018-09-20T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["2331-8325"]},"oa":1,"language":[{"iso":"eng"}],"keyword":["Platelets","Cell migration","Bacteria","Shear flow","Fibrinogen","E. coli"],"publication":"Bio-Protocol","has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"}],"month":"09","article_number":"e3018","acknowledgement":" FöFoLe project 947 (F.G.), the Friedrich-Baur-Stiftung project 41/16 (F.G.)","volume":8,"ddc":["570"],"date_updated":"2021-01-12T08:07:12Z","year":"2018","citation":{"ista":"Fan S, Lorenz M, Massberg S, Gärtner FR. 2018. Platelet migration and bacterial trapping assay under flow. Bio-Protocol. 8(18), e3018.","mla":"Fan, Shuxia, et al. “Platelet Migration and Bacterial Trapping Assay under Flow.” <i>Bio-Protocol</i>, vol. 8, no. 18, e3018, Bio-Protocol, 2018, doi:<a href=\"https://doi.org/10.21769/bioprotoc.3018\">10.21769/bioprotoc.3018</a>.","short":"S. Fan, M. Lorenz, S. Massberg, F.R. Gärtner, Bio-Protocol 8 (2018).","chicago":"Fan, Shuxia, Michael Lorenz, Steffen Massberg, and Florian R Gärtner. “Platelet Migration and Bacterial Trapping Assay under Flow.” <i>Bio-Protocol</i>. Bio-Protocol, 2018. <a href=\"https://doi.org/10.21769/bioprotoc.3018\">https://doi.org/10.21769/bioprotoc.3018</a>.","ieee":"S. Fan, M. Lorenz, S. Massberg, and F. R. Gärtner, “Platelet migration and bacterial trapping assay under flow,” <i>Bio-Protocol</i>, vol. 8, no. 18. Bio-Protocol, 2018.","ama":"Fan S, Lorenz M, Massberg S, Gärtner FR. Platelet migration and bacterial trapping assay under flow. <i>Bio-Protocol</i>. 2018;8(18). doi:<a href=\"https://doi.org/10.21769/bioprotoc.3018\">10.21769/bioprotoc.3018</a>","apa":"Fan, S., Lorenz, M., Massberg, S., &#38; Gärtner, F. R. (2018). Platelet migration and bacterial trapping assay under flow. <i>Bio-Protocol</i>. Bio-Protocol. <a href=\"https://doi.org/10.21769/bioprotoc.3018\">https://doi.org/10.21769/bioprotoc.3018</a>"},"doi":"10.21769/bioprotoc.3018","day":"20","abstract":[{"text":"Blood platelets are critical for hemostasis and thrombosis, but also play diverse roles during immune responses. We have recently reported that platelets migrate at sites of infection in vitro and in vivo. Importantly, platelets use their ability to migrate to collect and bundle fibrin (ogen)-bound bacteria accomplishing efficient intravascular bacterial trapping. Here, we describe a method that allows analyzing platelet migration in vitro, focusing on their ability to collect bacteria and trap bacteria under flow.","lang":"eng"}],"quality_controlled":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:47:28Z","publisher":"Bio-Protocol","_id":"6354","author":[{"last_name":"Fan","first_name":"Shuxia","full_name":"Fan, Shuxia"},{"full_name":"Lorenz, Michael","first_name":"Michael","last_name":"Lorenz"},{"full_name":"Massberg, Steffen","last_name":"Massberg","first_name":"Steffen"},{"first_name":"Florian R","last_name":"Gärtner","orcid":"0000-0001-6120-3723","full_name":"Gärtner, Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"}],"issue":"18","publication_status":"published","date_created":"2019-04-29T09:40:33Z","department":[{"_id":"MiSi"}],"title":"Platelet migration and bacterial trapping assay under flow","intvolume":"         8"}]