{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:39:15Z","timestamp":1790501955736,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"48","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["RECRUTE ANR-15-CE15-0022"],"award-info":[{"award-number":["RECRUTE ANR-15-CE15-0022"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ILIAAD ANR-18-CE09-0029"],"award-info":[{"award-number":["ILIAAD ANR-18-CE09-0029"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Amidex","award":["QantiQ 2016"],"award-info":[{"award-number":["QantiQ 2016"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,11,29]]},"abstract":"<jats:p>\n                    While cell migration can be directed by various mechanical cues such as force, deformation, stiffness, or flow, the associated mechanisms and functions may remain elusive. Single cell migration against flow, repeatedly reported with leukocytes, is arguably considered as active and mediated by integrin mechanotransduction, or passive and determined by a mechanical bias. Here, we reveal a phenotype of flow mechanotaxis with fish epithelial keratocytes that orient upstream or downstream at shear stresses around tens of dyn cm\n                    <jats:sup>\u22122<\/jats:sup>\n                    . We show that each cell has an intrinsic orientation that results from the mechanical interaction of flow with its morphology. The bulbous trailing edge of a keratocyte generates a hydrodynamical torque under flow that stabilizes an upstream orientation, just as the heavy lower edge of a roly-poly toy generates a gravitational torque that stabilizes an upright position. In turn, the wide and flat leading edge of keratocytes destabilizes upstream orientation, allowing the existence of two distinct phenotypes. To formalize these observations, we propose a simple mechanical model that considers keratocyte morphology as a hemisphere preceded by a wide thin sheet. Our findings show that this model can recapitulate the phase diagram of single cell orientation under flow without adjustable parameters. From a larger perspective, this passive mechanism of keratocytes flow mechanotaxis implies a potential absence of physiological function and evolution-driven process.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2210379119","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T15:18:11Z","timestamp":1669043891000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Keratocytes migrate against flow with a roly-poly-like mechanism"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1032-1516","authenticated-orcid":false,"given":"Valentine","family":"Seveau de Noray","sequence":"first","affiliation":[{"name":"Aix Marseille Universit\u00e9, CNRS, INSERM, Laboratoire Adhesion &amp; Inflammation, Turing Centre for Living Systems, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0926-948X","authenticated-orcid":false,"given":"Fabio","family":"Manca","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, CNRS, INSERM, Laboratoire Adhesion &amp; Inflammation, Turing Centre for Living Systems, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Mainil","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, CNRS, INSERM, Laboratoire Adhesion &amp; Inflammation, Turing Centre for Living Systems, 13009 Marseille, France"},{"name":"Mechanobiology &amp; Biomaterials group, Interfaces and Complex Fluids Laboratory, Research Institute for Biosciences, University of Mons, B-7000 Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6042-2294","authenticated-orcid":false,"given":"Alexandre","family":"Remson","sequence":"additional","affiliation":[{"name":"Mechanobiology &amp; Biomaterials group, Interfaces and Complex Fluids Laboratory, Research Institute for Biosciences, University of Mons, B-7000 Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Biarnes-Pelicot","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, CNRS, INSERM, Laboratoire Adhesion &amp; Inflammation, Turing Centre for Living Systems, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-8052","authenticated-orcid":false,"given":"Sylvain","family":"Gabriele","sequence":"additional","affiliation":[{"name":"Mechanobiology &amp; Biomaterials group, Interfaces and Complex Fluids Laboratory, Research Institute for Biosciences, University of Mons, B-7000 Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-3813","authenticated-orcid":false,"given":"Marie-Pierre","family":"Valignat","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, CNRS, INSERM, Laboratoire Adhesion &amp; Inflammation, Turing Centre for Living Systems, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-3709","authenticated-orcid":false,"given":"Olivier","family":"Theodoly","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, CNRS, INSERM, Laboratoire Adhesion &amp; Inflammation, Turing Centre for Living Systems, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00366-6"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/213256a0"},{"key":"e_1_3_5_3_2","first-page":"113","article-title":"Note sur la sensibilit\u00e9 des leucocytes \u00e0 l\u2019\u00e9lectricit\u00e9","volume":"18","author":"Dineur E.","year":"1891","unstructured":"E. Dineur, Note sur la sensibilit\u00e9 des leucocytes \u00e0 l\u2019\u00e9lectricit\u00e9. Bull S\u00e9ances Soc Belge Microsc.\u00a018,\u00a0113\u2013118 (1891).","journal-title":"Bull S\u00e9ances Soc Belge Microsc."},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.170679"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.03.051"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.12.007"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aat3178"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-12-3791"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317441110"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316848111"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.11.4502"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.11.011"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2018.04.008"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02523"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00726"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.3.H858"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103581108"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903732"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.625366"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4IB00201F"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.224204"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02482-4"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2019.1587269"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2019.08.044"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/intbio\/zyz034"},{"key":"e_1_3_5_26_2","doi-asserted-by":"crossref","unstructured":"N. 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