[{"abstract":[{"lang":"eng","text":"Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact."}],"author":[{"first_name":"Jana","full_name":"Slovakova, Jana","last_name":"Slovakova","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","full_name":"Sikora, Mateusz K","last_name":"Sikora","first_name":"Mateusz K"},{"orcid":"0000-0001-5809-9566","full_name":"Arslan, Feyza N","last_name":"Arslan","first_name":"Feyza N","id":"49DA7910-F248-11E8-B48F-1D18A9856A87"},{"id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","last_name":"Caballero Mancebo","full_name":"Caballero Mancebo, Silvia","orcid":"0000-0002-5223-3346","first_name":"Silvia"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","orcid":"0000-0003-4761-5996","last_name":"Krens","full_name":"Krens, Gabriel"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","full_name":"Kaufmann, Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin","full_name":"Merrin, Jack"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566"}],"citation":{"chicago":"Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences, 2022. <a href=\"https://doi.org/10.1073/pnas.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>.","apa":"Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens, G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>","ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8. Proceedings of the National Academy of Sciences, 2022.","ista":"Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. 119(8), e2122030119.","short":"J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W. Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","ama":"Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2022;119(8). doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8, e2122030119, Proceedings of the National Academy of Sciences, 2022, doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>."},"publication_status":"published","publication_identifier":{"eissn":["10916490"]},"_id":"10766","project":[{"grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Modulation of adhesion function in cell-cell contact formation by cortical tension","_id":"2521E28E-B435-11E9-9278-68D0E5697425","grant_number":"187-2013"}],"oa_version":"Published Version","quality_controlled":"1","acknowledgement":"We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo, and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour and Daniel Capek for help with data analysis. We also thank the Imaging & Optics, Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute of Science and Technology Austria (ISTA)Nasser Darwish-Miranda  for continuous support. We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.), Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced Grant (MECSPEC; to C.-P.H.).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","date_updated":"2023-08-02T14:26:51Z","oa":1,"volume":119,"external_id":{"isi":["000766926900009"]},"title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells","doi":"10.1073/pnas.2122030119","year":"2022","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"ec_funded":1,"related_material":{"record":[{"relation":"earlier_version","id":"9750","status":"public"}]},"ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"article_number":"e2122030119","isi":1,"intvolume":"       119","status":"public","day":"14","type":"journal_article","publication":"Proceedings of the National Academy of Sciences of the United States of America","issue":"8","file_date_updated":"2022-02-21T08:45:11Z","scopus_import":"1","publisher":"Proceedings of the National Academy of Sciences","language":[{"iso":"eng"}],"month":"02","date_published":"2022-02-14T00:00:00Z","article_type":"original","date_created":"2022-02-20T23:01:31Z","file":[{"date_created":"2022-02-21T08:45:11Z","checksum":"d49f83c3580613966f71768ddb9a55a5","file_name":"2022_PNAS_Slovakova.pdf","file_size":1609678,"date_updated":"2022-02-21T08:45:11Z","access_level":"open_access","success":1,"file_id":"10780","creator":"dernst","content_type":"application/pdf","relation":"main_file"}],"has_accepted_license":"1","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}]},{"year":"2020","month":"11","doi":"10.1101/2020.11.20.391284","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"SSU"}],"date_published":"2020-11-20T00:00:00Z","ec_funded":1,"title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion","publisher":"Cold Spring Harbor Laboratory","language":[{"iso":"eng"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.11.20.391284"}],"department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"related_material":{"record":[{"status":"public","relation":"later_version","id":"10766"},{"status":"public","id":"9623","relation":"dissertation_contains"}]},"date_created":"2021-07-29T11:29:50Z","citation":{"chicago":"Slovakova, Jana, Mateusz K Sikora, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Karla Huljev, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.11.20.391284\">https://doi.org/10.1101/2020.11.20.391284</a>.","apa":"Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W., Huljev, K., &#38; Heisenberg, C.-P. J. (2020). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.11.20.391284\">https://doi.org/10.1101/2020.11.20.391284</a>","ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","short":"J. Slovakova, M.K. Sikora, S. Caballero Mancebo, G. Krens, W. Kaufmann, K. Huljev, C.-P.J. Heisenberg, BioRxiv (2020).","ista":"Slovakova J, Sikora MK, Caballero Mancebo S, Krens G, Kaufmann W, Huljev K, Heisenberg C-PJ. 2020. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv, <a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>.","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>.","ama":"Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>"},"day":"20","publication_status":"published","type":"preprint","abstract":[{"text":"Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.","lang":"eng"}],"status":"public","author":[{"first_name":"Jana","full_name":"Slovakova, Jana","last_name":"Slovakova","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","last_name":"Sikora","full_name":"Sikora, Mateusz K","first_name":"Mateusz K"},{"last_name":"Caballero Mancebo","full_name":"Caballero Mancebo, Silvia","orcid":"0000-0002-5223-3346","first_name":"Silvia","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","last_name":"Krens","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","first_name":"Gabriel"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","full_name":"Kaufmann, Walter","first_name":"Walter"},{"last_name":"Huljev","full_name":"Huljev, Karla","first_name":"Karla","id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"publication":"bioRxiv","page":"41","article_processing_charge":"No","date_updated":"2024-03-25T23:30:10Z","oa":1,"_id":"9750","oa_version":"Preprint","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"},{"grant_number":"187-2013","_id":"2521E28E-B435-11E9-9278-68D0E5697425","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","acknowledgement":"We would like to thank Edouard Hannezo for discussions, Shayan Shami Pour and Daniel Capek for help with data analysis, Vanessa Barone and other members of the Heisenberg laboratory for thoughtful discussions and comments on the manuscript. We also thank Jack Merrin for preparing the microwells, and the Scientific Service Units at IST Austria, specifically Bioimaging and Electron Microscopy, and the Zebrafish Facility for continuous support. We acknowledge Hitoshi Morita for the kind gift of VinculinB-GFP plasmid. This research was supported by an ERC Advanced Grant (MECSPEC) to C.-P.H, EMBO Long Term grant (ALTF 187-2013) to M.S and IST Fellow Marie-Curie COFUND No. P_IST_EU01 to J.S."}]