Dynamic Rigidity Changes Enable Rapid Cell Migration on Soft Substrates

Dynamic Rigidity Changes Enable Rapid Cell Migration on Soft Substrates | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Dynamic Rigidity Changes Enable Rapid Cell Migration on Soft Substrates Yi Cao, Jiapeng Yang, Yu Zhang, Shuo Wang, Peng Wang, Liang Dong, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5225113/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Oct, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Cell migration is crucial in various biological processes, regulated by surrounding rigidity. Studies under static conditions suggest migration favors rigid substrates, as softer substrates (< 4 kPa) do not provide sufficient traction forces. Here we show that mesenchymal stem cells (MSCs) can overcome this limitation when exposed to rapid cyclic changes in substrate rigidity. Under dynamic conditions, cell traction forces progressively rise, promoting a swift mechanical turnover of focal adhesions. This adaptation obviates the need for cell polarity and the mechanochemical turnover of focal adhesions typically required for traditional mesenchymal-type migration. The rapid migration speed together with the shape evolution during migration can be adequately predicted by our theoretical model that considering the force balance under dynamic conditions. Our findings underscore the innate capacity of cells to navigate through fluctuating mechanical cues, highlighting a versatile cellular response mechanism for understanding cell behaviors under dynamic physiological or pathological conditions. Biological sciences/Cell biology/Cell migration/Extracellular matrix Biological sciences/Biophysics/Motility/Cellular motility Biological sciences/Cell biology/Cell migration/Focal adhesion Physical sciences/Materials science/Soft materials/Gels and hydrogels Biological sciences/Cell biology/Cell adhesion/Mechanotransduction cell migration cyclic change in substrate rigidity mechanotransduction cell force focal adhesion Myosin mesenchymal stem cell molecular clutch Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMovie11.mp4 Supplementary Movie 11 SupplementaryMovie4.mp4 Supplementary Movie 4 SupplementaryMovie2.mp4 Supplementary Movie 2 SupplementaryMovie9.mp4 Supplementary Movie 9 nrreportingsummary.pdf Reporting Summary SupplementaryMovie8.mp4 Supplementary Movie 8 SupplementaryMovie10.mp4 Supplementary Movie 10 SupplementaryMovie18.mp4 Supplementary Movie 18 BioRenderPublicationLicense.pdf BioRender Publication License AuthorChecklistNCOMMS2474023BCao175369213138.docx Author Checklist SupplementaryMovie20.mp4 Supplementary Movie 20 SupplementaryMovie16.mp4 Supplementary Movie 16 InventoryofSupportingInformation.docx Inventory of Supporting Information SupplementaryMovie21.mp4 Supplementary Movie 21 nreditorialpolicychecklist.pdf Editorial Policy Checklist SupplementaryMovie12.mp4 Supplementary Movie 12 SourceData.xlsx Source Data SupplementaryMovie1.mp4 Supplementary Movie 1 SupplementaryMovie17.mp4 Supplementary Movie 17 SupplementaryMovie15.mp4 Supplementary Movie 15 SupplementaryMovie5.mp4 Supplementary Movie 5 SupplementaryMovie13.mp4 Supplementary Movie 13 SupplementaryMovie19.mp4 Supplementary Movie 19 SupplementaryMovie14.mp4 Supplementary Movie 14 SupplementaryMovie7.mp4 Supplementary Movie 7 SupplementaryMovie3.mp4 Supplementary Movie 3 SupplementaryInformation.pdf Supplementary Information SupplementaryMovie6.mp4 Supplementary Movie 6 NCOMMS2474023CSignedConsentforAuthorOrderChange.docx Signed Consent for Author Order Change SupplementaryInformation.pdf Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 02 Oct, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5225113","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":499337765,"identity":"b69f1468-f4bb-4bf5-9ee2-2fc7505cd993","order_by":0,"name":"Yi 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Substrates","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cell migration, cyclic change in substrate rigidity, mechanotransduction, cell force, focal adhesion, Myosin, mesenchymal stem cell, molecular clutch","lastPublishedDoi":"10.21203/rs.3.rs-5225113/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5225113/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCell migration is crucial in various biological processes, regulated by surrounding rigidity. Studies under static conditions suggest migration favors rigid substrates, as softer substrates (\u0026lt;\u0026thinsp;4 kPa) do not provide sufficient traction forces. Here we show that mesenchymal stem cells (MSCs) can overcome this limitation when exposed to rapid cyclic changes in substrate rigidity. Under dynamic conditions, cell traction forces progressively rise, promoting a swift mechanical turnover of focal adhesions. This adaptation obviates the need for cell polarity and the mechanochemical turnover of focal adhesions typically required for traditional mesenchymal-type migration. The rapid migration speed together with the shape evolution during migration can be adequately predicted by our theoretical model that considering the force balance under dynamic conditions. Our findings underscore the innate capacity of cells to navigate through fluctuating mechanical cues, highlighting a versatile cellular response mechanism for understanding cell behaviors under dynamic physiological or pathological conditions.\u003c/p\u003e","manuscriptTitle":"Dynamic Rigidity Changes Enable Rapid Cell Migration on Soft Substrates","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-19 16:34:44","doi":"10.21203/rs.3.rs-5225113/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5fc0e147-c0fe-4d4a-b8fc-b7f11863519d","owner":[],"postedDate":"August 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":53038069,"name":"Biological sciences/Cell biology/Cell migration/Extracellular matrix"},{"id":53038070,"name":"Biological sciences/Biophysics/Motility/Cellular motility"},{"id":53038071,"name":"Biological sciences/Cell biology/Cell migration/Focal adhesion"},{"id":53038072,"name":"Physical sciences/Materials science/Soft materials/Gels and hydrogels"},{"id":53038073,"name":"Biological sciences/Cell biology/Cell adhesion/Mechanotransduction"}],"tags":[],"updatedAt":"2025-10-03T07:06:32+00:00","versionOfRecord":{"articleIdentity":"rs-5225113","link":"https://doi.org/10.1038/s41467-025-63854-9","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2025-10-02 04:00:00","publishedOnDateReadable":"October 2nd, 2025"},"versionCreatedAt":"2025-08-19 16:34:44","video":"","vorDoi":"10.1038/s41467-025-63854-9","vorDoiUrl":"https://doi.org/10.1038/s41467-025-63854-9","workflowStages":[]},"version":"v1","identity":"rs-5225113","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5225113","identity":"rs-5225113","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}