[{"day":"14","publication":"Proceedings of the National Academy of Sciences of the United States of America","isi":1,"has_accepted_license":"1","year":"2022","date_published":"2022-02-14T00:00:00Z","doi":"10.1073/pnas.2122030119","date_created":"2022-02-20T23:01:31Z","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.).","quality_controlled":"1","publisher":"Proceedings of the National Academy of Sciences","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Slovakova, Jana, et al. “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, vol. 119, no. 8, e2122030119, Proceedings of the National Academy of Sciences, 2022, doi:10.1073/pnas.2122030119.","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).","ieee":"J. Slovakova et al., “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, vol. 119, no. 8. Proceedings of the National Academy of Sciences, 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. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(8). doi:10.1073/pnas.2122030119","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. Proceedings of the National Academy of Sciences of the United States of America. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2122030119","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.” Proceedings of the National Academy of Sciences of the United States of America. Proceedings of the National Academy of Sciences, 2022. https://doi.org/10.1073/pnas.2122030119.","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."},"title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells","author":[{"full_name":"Slovakova, Jana","last_name":"Slovakova","first_name":"Jana","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sikora, Mateusz K","last_name":"Sikora","first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5809-9566","full_name":"Arslan, Feyza N","last_name":"Arslan","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","first_name":"Feyza N"},{"orcid":"0000-0002-5223-3346","full_name":"Caballero Mancebo, Silvia","last_name":"Caballero Mancebo","first_name":"Silvia","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","last_name":"Krens"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter"},{"orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","last_name":"Merrin","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000766926900009"]},"article_processing_charge":"No","article_number":"e2122030119","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"},{"_id":"2521E28E-B435-11E9-9278-68D0E5697425","grant_number":"187-2013","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension"}],"file":[{"success":1,"checksum":"d49f83c3580613966f71768ddb9a55a5","file_id":"10780","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2022_PNAS_Slovakova.pdf","date_created":"2022-02-21T08:45:11Z","file_size":1609678,"date_updated":"2022-02-21T08:45:11Z","creator":"dernst"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["10916490"]},"publication_status":"published","related_material":{"record":[{"relation":"earlier_version","status":"public","id":"9750"}]},"volume":119,"issue":"8","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","oa_version":"Published Version","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."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"month":"02","intvolume":" 119","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-02T14:26:51Z","file_date_updated":"2022-02-21T08:45:11Z","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"_id":"10766","status":"public","article_type":"original","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"}},{"_id":"8680","article_type":"original","type":"journal_article","keyword":["Multidisciplinary"],"status":"public","date_updated":"2023-08-22T10:36:35Z","department":[{"_id":"CaHe"}],"abstract":[{"text":"Animal development entails the organization of specific cell types in space and time, and spatial patterns must form in a robust manner. In the zebrafish spinal cord, neural progenitors form stereotypic patterns despite noisy morphogen signaling and large-scale cellular rearrangements during morphogenesis and growth. By directly measuring adhesion forces and preferences for three types of endogenous neural progenitors, we provide evidence for the differential adhesion model in which differences in intercellular adhesion mediate cell sorting. Cell type–specific combinatorial expression of different classes of cadherins (N-cadherin, cadherin 11, and protocadherin 19) results in homotypic preference ex vivo and patterning robustness in vivo. Furthermore, the differential adhesion code is regulated by the sonic hedgehog morphogen gradient. We propose that robust patterning during tissue morphogenesis results from interplay between adhesion-based self-organization and morphogen-directed patterning.","lang":"eng"}],"oa_version":"Preprint","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/803635v1"}],"scopus_import":"1","intvolume":" 370","month":"10","publication_status":"published","publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"language":[{"iso":"eng"}],"ec_funded":1,"volume":370,"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/sticking-together/"}]},"issue":"6512","project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425"}],"citation":{"ista":"Tsai TY-C, Sikora MK, Xia P, Colak-Champollion T, Knaut H, Heisenberg C-PJ, Megason SG. 2020. An adhesion code ensures robust pattern formation during tissue morphogenesis. Science. 370(6512), 113–116.","chicago":"Tsai, Tony Y.-C., Mateusz K Sikora, Peng Xia, Tugba Colak-Champollion, Holger Knaut, Carl-Philipp J Heisenberg, and Sean G. Megason. “An Adhesion Code Ensures Robust Pattern Formation during Tissue Morphogenesis.” Science. American Association for the Advancement of Science, 2020. https://doi.org/10.1126/science.aba6637.","short":"T.Y.-C. Tsai, M.K. Sikora, P. Xia, T. Colak-Champollion, H. Knaut, C.-P.J. Heisenberg, S.G. Megason, Science 370 (2020) 113–116.","ieee":"T. Y.-C. Tsai et al., “An adhesion code ensures robust pattern formation during tissue morphogenesis,” Science, vol. 370, no. 6512. American Association for the Advancement of Science, pp. 113–116, 2020.","apa":"Tsai, T. Y.-C., Sikora, M. K., Xia, P., Colak-Champollion, T., Knaut, H., Heisenberg, C.-P. J., & Megason, S. G. (2020). An adhesion code ensures robust pattern formation during tissue morphogenesis. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aba6637","ama":"Tsai TY-C, Sikora MK, Xia P, et al. An adhesion code ensures robust pattern formation during tissue morphogenesis. Science. 2020;370(6512):113-116. doi:10.1126/science.aba6637","mla":"Tsai, Tony Y. C., et al. “An Adhesion Code Ensures Robust Pattern Formation during Tissue Morphogenesis.” Science, vol. 370, no. 6512, American Association for the Advancement of Science, 2020, pp. 113–16, doi:10.1126/science.aba6637."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000579169000053"]},"article_processing_charge":"No","author":[{"full_name":"Tsai, Tony Y.-C.","last_name":"Tsai","first_name":"Tony Y.-C."},{"full_name":"Sikora, Mateusz K","last_name":"Sikora","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K"},{"last_name":"Xia","orcid":"0000-0002-5419-7756","full_name":"Xia, Peng","id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","first_name":"Peng"},{"first_name":"Tugba","full_name":"Colak-Champollion, Tugba","last_name":"Colak-Champollion"},{"full_name":"Knaut, Holger","last_name":"Knaut","first_name":"Holger"},{"last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Megason, Sean G.","last_name":"Megason","first_name":"Sean G."}],"title":"An adhesion code ensures robust pattern formation during tissue morphogenesis","acknowledgement":"We thank the members of the Megason and Heisenberg labs for critical discussions of and technical assistance during the work and B. Appel, S. Holley, J. Jontes, and D. Gilmour for transgenic fish. This work is supported by the Damon Runyon Cancer Foundation, a NICHD K99 fellowship (1K99HD092623), a Travelling Fellowship of the Company of Biologists, a Collaborative Research grant from the Burroughs Wellcome Foundation (T.Y.-C.T.), NIH grant 01GM107733 (T.Y.-C.T. and S.G.M.), NIH grant R01NS102322 (T.C.-C. and H.K.), and an ERC advanced grant\r\n(MECSPEC) (C.-P.H.).","oa":1,"publisher":"American Association for the Advancement of Science","quality_controlled":"1","year":"2020","isi":1,"publication":"Science","day":"02","page":"113-116","date_created":"2020-10-19T14:09:38Z","date_published":"2020-10-02T00:00:00Z","doi":"10.1126/science.aba6637"},{"ec_funded":1,"date_created":"2021-07-29T11:29:50Z","doi":"10.1101/2020.11.20.391284","related_material":{"record":[{"relation":"later_version","status":"public","id":"10766"},{"status":"public","id":"9623","relation":"dissertation_contains"}]},"date_published":"2020-11-20T00:00:00Z","page":"41","publication":"bioRxiv","language":[{"iso":"eng"}],"day":"20","year":"2020","publication_status":"published","month":"11","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2020.11.20.391284","open_access":"1"}],"publisher":"Cold Spring Harbor Laboratory","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.","oa_version":"Preprint","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 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."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"SSU"}],"title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"article_processing_charge":"No","author":[{"first_name":"Jana","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87","last_name":"Slovakova","full_name":"Slovakova, Jana"},{"first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","full_name":"Sikora, Mateusz K","last_name":"Sikora"},{"orcid":"0000-0002-5223-3346","full_name":"Caballero Mancebo, Silvia","last_name":"Caballero Mancebo","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","first_name":"Silvia"},{"full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","last_name":"Krens","first_name":"Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kaufmann","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Karla","id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87","full_name":"Huljev, Karla","last_name":"Huljev"},{"first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.11.20.391284.","apa":"Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W., Huljev, K., & Heisenberg, C.-P. J. (2020). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.11.20.391284","ama":"Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv. 2020. doi:10.1101/2020.11.20.391284","ieee":"J. Slovakova et al., “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion,” bioRxiv. 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).","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.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.11.20.391284.","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, 10.1101/2020.11.20.391284."},"date_updated":"2024-03-27T23:30:18Z","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573"},{"name":"Modulation of adhesion function in cell-cell contact formation by cortical tension","grant_number":"187-2013","_id":"2521E28E-B435-11E9-9278-68D0E5697425"}],"status":"public","type":"preprint","_id":"9750"},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Schmalhorst, Philipp S., et al. “Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides.” Journal of Chemical Theory and Computation, vol. 13, no. 10, American Chemical Society, 2017, pp. 5039–53, doi:10.1021/acs.jctc.7b00374.","ieee":"P. S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P. J. Heisenberg, and M. K. Sikora, “Overcoming the limitations of the MARTINI force field in simulations of polysaccharides,” Journal of Chemical Theory and Computation, vol. 13, no. 10. American Chemical Society, pp. 5039–5053, 2017.","short":"P.S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P.J. Heisenberg, M.K. Sikora, Journal of Chemical Theory and Computation 13 (2017) 5039–5053.","ama":"Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. 2017;13(10):5039-5053. doi:10.1021/acs.jctc.7b00374","apa":"Schmalhorst, P. S., Deluweit, F., Scherrers, R., Heisenberg, C.-P. J., & Sikora, M. K. (2017). Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. American Chemical Society. https://doi.org/10.1021/acs.jctc.7b00374","chicago":"Schmalhorst, Philipp S, Felix Deluweit, Roger Scherrers, Carl-Philipp J Heisenberg, and Mateusz K Sikora. “Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides.” Journal of Chemical Theory and Computation. American Chemical Society, 2017. https://doi.org/10.1021/acs.jctc.7b00374.","ista":"Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. 2017. Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. 13(10), 5039–5053."},"title":"Overcoming the limitations of the MARTINI force field in simulations of polysaccharides","author":[{"first_name":"Philipp S","id":"309D50DA-F248-11E8-B48F-1D18A9856A87","full_name":"Schmalhorst, Philipp S","orcid":"0000-0002-5795-0133","last_name":"Schmalhorst"},{"first_name":"Felix","last_name":"Deluweit","full_name":"Deluweit, Felix"},{"full_name":"Scherrers, Roger","last_name":"Scherrers","first_name":"Roger"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg"},{"first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","full_name":"Sikora, Mateusz K","last_name":"Sikora"}],"publist_id":"6847","external_id":{"isi":["000412965700036"]},"article_processing_charge":"No","day":"10","publication":"Journal of Chemical Theory and Computation","isi":1,"year":"2017","date_published":"2017-10-10T00:00:00Z","doi":"10.1021/acs.jctc.7b00374","date_created":"2018-12-11T11:48:35Z","page":"5039 - 5053","acknowledgement":"P.S.S. was supported by research fellowship 2811/1-1 from the German Research Foundation (DFG), and M.S. was supported by EMBO Long Term Fellowship ALTF 187-2013 and Grant GC65-32 from the Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), University of Warsaw, Poland. The authors thank Antje Potthast, Marek Cieplak, Tomasz Włodarski, and Damien Thompson for fruitful discussions and the IST Austria Scientific Computing Facility for support.","publisher":"American Chemical Society","quality_controlled":"1","oa":1,"date_updated":"2023-09-27T10:58:45Z","department":[{"_id":"CaHe"}],"_id":"804","status":"public","type":"journal_article","language":[{"iso":"eng"}],"publication_identifier":{"issn":["15499618"]},"publication_status":"published","issue":"10","volume":13,"oa_version":"Submitted Version","abstract":[{"lang":"eng","text":"Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides."}],"acknowledged_ssus":[{"_id":"ScienComp"}],"month":"10","intvolume":" 13","scopus_import":"1","main_file_link":[{"url":"https://arxiv.org/abs/1704.03773","open_access":"1"}]},{"isi":1,"year":"2017","day":"23","publication":"Developmental Cell","page":"198 - 211","doi":"10.1016/j.devcel.2017.09.014","date_published":"2017-10-23T00:00:00Z","date_created":"2018-12-11T11:48:13Z","quality_controlled":"1","publisher":"Cell Press","citation":{"chicago":"Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.","ista":"Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211.","mla":"Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014.","ieee":"V. Barone et al., “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” Developmental Cell, vol. 43, no. 2. Cell Press, pp. 198–211, 2017.","short":"V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.","ama":"Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014","apa":"Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2017.09.014"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"orcid":"0000-0003-2676-3367","full_name":"Barone, Vanessa","last_name":"Barone","first_name":"Vanessa","id":"419EECCC-F248-11E8-B48F-1D18A9856A87"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","full_name":"Lang, Moritz","last_name":"Lang"},{"last_name":"Krens","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel"},{"first_name":"Saurabh","full_name":"Pradhan, Saurabh","last_name":"Pradhan"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","first_name":"Shayan","last_name":"Shamipour","full_name":"Shamipour, Shayan"},{"id":"3BED66BE-F248-11E8-B48F-1D18A9856A87","first_name":"Keisuke","orcid":"0000-0002-6453-8075","full_name":"Sako, Keisuke","last_name":"Sako"},{"full_name":"Sikora, Mateusz K","last_name":"Sikora","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J"}],"publist_id":"6934","article_processing_charge":"No","external_id":{"isi":["000413443700011"]},"title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"name":"Cell segregation in gastrulation: the role of cell fate specification","grant_number":"I2058","_id":"252DD2A6-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"publication_identifier":{"issn":["15345807"]},"publication_status":"published","language":[{"iso":"eng"}],"issue":"2","related_material":{"record":[{"status":"public","id":"961","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"8350"}]},"volume":43,"ec_funded":1,"abstract":[{"text":"Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.","lang":"eng"}],"oa_version":"None","scopus_import":"1","month":"10","intvolume":" 43","date_updated":"2024-03-27T23:30:38Z","department":[{"_id":"CaHe"},{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"735","type":"journal_article","status":"public"},{"month":"06","intvolume":" 37","scopus_import":1,"publisher":"Cell Press","quality_controlled":"1","oa_version":"None","volume":37,"related_material":{"record":[{"id":"7186","status":"public","relation":"part_of_dissertation"}]},"doi":"10.1016/j.devcel.2016.05.024","issue":"6","date_published":"2016-06-20T00:00:00Z","date_created":"2018-12-11T11:50:07Z","page":"493 - 506","day":"20","language":[{"iso":"eng"}],"publication":"Developmental Cell","publication_status":"published","year":"2016","status":"public","type":"journal_article","_id":"1096","title":"Actin rings of power","department":[{"_id":"CaHe"}],"publist_id":"6279","author":[{"last_name":"Schwayer","full_name":"Schwayer, Cornelia","orcid":"0000-0001-5130-2226","first_name":"Cornelia","id":"3436488C-F248-11E8-B48F-1D18A9856A87"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K","last_name":"Sikora","full_name":"Sikora, Mateusz K"},{"last_name":"Slovakova","full_name":"Slovakova, Jana","first_name":"Jana","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kardos","full_name":"Kardos, Roland","id":"4039350E-F248-11E8-B48F-1D18A9856A87","first_name":"Roland"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2023-09-07T12:56:41Z","citation":{"mla":"Schwayer, Cornelia, et al. “Actin Rings of Power.” Developmental Cell, vol. 37, no. 6, Cell Press, 2016, pp. 493–506, doi:10.1016/j.devcel.2016.05.024.","ama":"Schwayer C, Sikora MK, Slovakova J, Kardos R, Heisenberg C-PJ. Actin rings of power. Developmental Cell. 2016;37(6):493-506. doi:10.1016/j.devcel.2016.05.024","apa":"Schwayer, C., Sikora, M. K., Slovakova, J., Kardos, R., & Heisenberg, C.-P. J. (2016). Actin rings of power. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2016.05.024","ieee":"C. Schwayer, M. K. Sikora, J. Slovakova, R. Kardos, and C.-P. J. Heisenberg, “Actin rings of power,” Developmental Cell, vol. 37, no. 6. Cell Press, pp. 493–506, 2016.","short":"C. Schwayer, M.K. Sikora, J. Slovakova, R. Kardos, C.-P.J. Heisenberg, Developmental Cell 37 (2016) 493–506.","chicago":"Schwayer, Cornelia, Mateusz K Sikora, Jana Slovakova, Roland Kardos, and Carl-Philipp J Heisenberg. “Actin Rings of Power.” Developmental Cell. Cell Press, 2016. https://doi.org/10.1016/j.devcel.2016.05.024.","ista":"Schwayer C, Sikora MK, Slovakova J, Kardos R, Heisenberg C-PJ. 2016. Actin rings of power. Developmental Cell. 37(6), 493–506."}},{"department":[{"_id":"CaHe"}],"file_date_updated":"2020-07-14T12:45:02Z","ddc":["570"],"date_updated":"2023-02-23T14:05:55Z","status":"public","pubrep_id":"478","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"1566","volume":11,"related_material":{"record":[{"relation":"research_data","id":"9714","status":"public"}]},"issue":"10","file":[{"date_created":"2018-12-12T10:16:21Z","file_name":"IST-2016-478-v1+1_journal.pcbi.1004541.pdf","creator":"system","date_updated":"2020-07-14T12:45:02Z","file_size":1412511,"checksum":"8b67d729be663bfc9af04bfd94459655","file_id":"5207","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_status":"published","month":"10","intvolume":" 11","scopus_import":1,"oa_version":"Published Version","abstract":[{"text":"Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease.","lang":"eng"}],"title":"An exploration of the universe of polyglutamine structures","author":[{"full_name":"Gómez Sicilia, Àngel","last_name":"Gómez Sicilia","first_name":"Àngel"},{"first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","full_name":"Sikora, Mateusz K","last_name":"Sikora"},{"last_name":"Cieplak","full_name":"Cieplak, Marek","first_name":"Marek"},{"last_name":"Carrión Vázquez","full_name":"Carrión Vázquez, Mariano","first_name":"Mariano"}],"publist_id":"5605","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Gómez Sicilia, Àngel, et al. “An Exploration of the Universe of Polyglutamine Structures.” PLoS Computational Biology, vol. 11, no. 10, e1004541, Public Library of Science, 2015, doi:10.1371/journal.pcbi.1004541.","apa":"Gómez Sicilia, À., Sikora, M. K., Cieplak, M., & Carrión Vázquez, M. (2015). An exploration of the universe of polyglutamine structures. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1004541","ama":"Gómez Sicilia À, Sikora MK, Cieplak M, Carrión Vázquez M. An exploration of the universe of polyglutamine structures. PLoS Computational Biology. 2015;11(10). doi:10.1371/journal.pcbi.1004541","ieee":"À. Gómez Sicilia, M. K. Sikora, M. Cieplak, and M. Carrión Vázquez, “An exploration of the universe of polyglutamine structures,” PLoS Computational Biology, vol. 11, no. 10. Public Library of Science, 2015.","short":"À. Gómez Sicilia, M.K. Sikora, M. Cieplak, M. Carrión Vázquez, PLoS Computational Biology 11 (2015).","chicago":"Gómez Sicilia, Àngel, Mateusz K Sikora, Marek Cieplak, and Mariano Carrión Vázquez. “An Exploration of the Universe of Polyglutamine Structures.” PLoS Computational Biology. Public Library of Science, 2015. https://doi.org/10.1371/journal.pcbi.1004541.","ista":"Gómez Sicilia À, Sikora MK, Cieplak M, Carrión Vázquez M. 2015. An exploration of the universe of polyglutamine structures. PLoS Computational Biology. 11(10), e1004541."},"article_number":"e1004541","date_published":"2015-10-23T00:00:00Z","doi":"10.1371/journal.pcbi.1004541","date_created":"2018-12-11T11:52:45Z","day":"23","publication":"PLoS Computational Biology","has_accepted_license":"1","year":"2015","publisher":"Public Library of Science","quality_controlled":"1","oa":1,"acknowledgement":"We acknowledge the support by the EU Joint Programme in Neurodegenerative Diseases (JPND AC14/00037) project. The project is supported through the following funding organisations under the aegis of JPND—www.jpnd.eu: Ireland, HRB; Poland, National Science Centre; and Spain, ISCIII. "},{"oa_version":"Published Version","publisher":"Public Library of Science ","month":"10","year":"2015","day":"23","date_created":"2021-07-23T12:05:28Z","doi":"10.1371/journal.pcbi.1004541.s001","date_published":"2015-10-23T00:00:00Z","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"1566"}]},"_id":"9714","type":"research_data_reference","status":"public","date_updated":"2023-02-23T10:04:35Z","citation":{"short":"À. Gómez Sicilia, M.K. Sikora, M. Cieplak, M. Carrión Vázquez, (2015).","ieee":"À. Gómez Sicilia, M. K. Sikora, M. Cieplak, and M. Carrión Vázquez, “An exploration of the universe of polyglutamine structures - submission to PLOS journals.” Public Library of Science , 2015.","apa":"Gómez Sicilia, À., Sikora, M. K., Cieplak, M., & Carrión Vázquez, M. (2015). An exploration of the universe of polyglutamine structures - submission to PLOS journals. Public Library of Science . https://doi.org/10.1371/journal.pcbi.1004541.s001","ama":"Gómez Sicilia À, Sikora MK, Cieplak M, Carrión Vázquez M. An exploration of the universe of polyglutamine structures - submission to PLOS journals. 2015. doi:10.1371/journal.pcbi.1004541.s001","mla":"Gómez Sicilia, Àngel, et al. An Exploration of the Universe of Polyglutamine Structures - Submission to PLOS Journals. Public Library of Science , 2015, doi:10.1371/journal.pcbi.1004541.s001.","ista":"Gómez Sicilia À, Sikora MK, Cieplak M, Carrión Vázquez M. 2015. An exploration of the universe of polyglutamine structures - submission to PLOS journals, Public Library of Science , 10.1371/journal.pcbi.1004541.s001.","chicago":"Gómez Sicilia, Àngel, Mateusz K Sikora, Marek Cieplak, and Mariano Carrión Vázquez. “An Exploration of the Universe of Polyglutamine Structures - Submission to PLOS Journals.” Public Library of Science , 2015. https://doi.org/10.1371/journal.pcbi.1004541.s001."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","article_processing_charge":"No","author":[{"first_name":"Àngel","full_name":"Gómez Sicilia, Àngel","last_name":"Gómez Sicilia"},{"full_name":"Sikora, Mateusz K","last_name":"Sikora","first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Marek","full_name":"Cieplak, Marek","last_name":"Cieplak"},{"first_name":"Mariano","last_name":"Carrión Vázquez","full_name":"Carrión Vázquez, Mariano"}],"title":"An exploration of the universe of polyglutamine structures - submission to PLOS journals","department":[{"_id":"CaHe"}]},{"author":[{"full_name":"Chwastyk, Mateusz","last_name":"Chwastyk","first_name":"Mateusz"},{"full_name":"Galera Prat, Albert","last_name":"Galera Prat","first_name":"Albert"},{"last_name":"Sikora","full_name":"Sikora, Mateusz K","first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gómez Sicilia","full_name":"Gómez Sicilia, Àngel","first_name":"Àngel"},{"first_name":"Mariano","last_name":"Carrión Vázquez","full_name":"Carrión Vázquez, Mariano"},{"full_name":"Cieplak, Marek","last_name":"Cieplak","first_name":"Marek"}],"publist_id":"5204","title":"Theoretical tests of the mechanical protection strategy in protein nanomechanics","department":[{"_id":"CaHe"}],"date_updated":"2021-01-12T06:53:52Z","citation":{"chicago":"Chwastyk, Mateusz, Albert Galera Prat, Mateusz K Sikora, Àngel Gómez Sicilia, Mariano Carrión Vázquez, and Marek Cieplak. “Theoretical Tests of the Mechanical Protection Strategy in Protein Nanomechanics.” Proteins: Structure, Function and Bioinformatics. Wiley-Blackwell, 2014. https://doi.org/10.1002/prot.24436.","ista":"Chwastyk M, Galera Prat A, Sikora MK, Gómez Sicilia À, Carrión Vázquez M, Cieplak M. 2014. Theoretical tests of the mechanical protection strategy in protein nanomechanics. Proteins: Structure, Function and Bioinformatics. 82(5), 717–726.","mla":"Chwastyk, Mateusz, et al. “Theoretical Tests of the Mechanical Protection Strategy in Protein Nanomechanics.” Proteins: Structure, Function and Bioinformatics, vol. 82, no. 5, Wiley-Blackwell, 2014, pp. 717–26, doi:10.1002/prot.24436.","ama":"Chwastyk M, Galera Prat A, Sikora MK, Gómez Sicilia À, Carrión Vázquez M, Cieplak M. Theoretical tests of the mechanical protection strategy in protein nanomechanics. Proteins: Structure, Function and Bioinformatics. 2014;82(5):717-726. doi:10.1002/prot.24436","apa":"Chwastyk, M., Galera Prat, A., Sikora, M. K., Gómez Sicilia, À., Carrión Vázquez, M., & Cieplak, M. (2014). Theoretical tests of the mechanical protection strategy in protein nanomechanics. Proteins: Structure, Function and Bioinformatics. Wiley-Blackwell. https://doi.org/10.1002/prot.24436","ieee":"M. Chwastyk, A. Galera Prat, M. K. Sikora, À. Gómez Sicilia, M. Carrión Vázquez, and M. Cieplak, “Theoretical tests of the mechanical protection strategy in protein nanomechanics,” Proteins: Structure, Function and Bioinformatics, vol. 82, no. 5. Wiley-Blackwell, pp. 717–726, 2014.","short":"M. Chwastyk, A. Galera Prat, M.K. Sikora, À. Gómez Sicilia, M. Carrión Vázquez, M. Cieplak, Proteins: Structure, Function and Bioinformatics 82 (2014) 717–726."},"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","type":"journal_article","status":"public","_id":"1891","page":"717 - 726","date_created":"2018-12-11T11:54:34Z","volume":82,"doi":"10.1002/prot.24436","date_published":"2014-05-01T00:00:00Z","issue":"5","year":"2014","publication_status":"published","language":[{"iso":"eng"}],"publication":"Proteins: Structure, Function and Bioinformatics","day":"01","scopus_import":1,"publisher":"Wiley-Blackwell","intvolume":" 82","month":"05","abstract":[{"lang":"eng","text":"We provide theoretical tests of a novel experimental technique to determine mechanostability of proteins based on stretching a mechanically protected protein by single-molecule force spectroscopy. This technique involves stretching a homogeneous or heterogeneous chain of reference proteins (single-molecule markers) in which one of them acts as host to the guest protein under study. The guest protein is grafted into the host through genetic engineering. It is expected that unraveling of the host precedes the unraveling of the guest removing ambiguities in the reading of the force-extension patterns of the guest protein. We study examples of such systems within a coarse-grained structure-based model. We consider systems with various ratios of mechanostability for the host and guest molecules and compare them to experimental results involving cohesin I as the guest molecule. For a comparison, we also study the force-displacement patterns in proteins that are linked in a serial fashion. We find that the mechanostability of the guest is similar to that of the isolated or serially linked protein. We also demonstrate that the ideal configuration of this strategy would be one in which the host is much more mechanostable than the single-molecule markers. We finally show that it is troublesome to use the highly stable cystine knot proteins as a host to graft a guest in stretching studies because this would involve a cleaving procedure."}],"acknowledgement":"Grant Nr. 2011/01/N/ST3/02475","oa_version":"None"}]