Collective migration of epithelial cells in the presence of regularly spaced obstacles

Collective migration of epithelial cells in the presence of regularly spaced obstacles | 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 Collective migration of epithelial cells in the presence of regularly spaced obstacles Andreas Janshoff, Tanmaya Sethi, Paul Nieschwitz, Alf Honigmann, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5982549/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Oct, 2025 Read the published version in Communications Physics → Version 1 posted You are reading this latest preprint version Abstract Physical confinement plays a crucial role in tissue development, creating a microenvironment and contributing to tumorigenesis. We investigate how physical confinement affects the collective behavior of Madin-Darby Canine Kidney (MDCK) II epithelial monolayers by introducing regularly spaced adhesive micropillars as stiff adhesive obstacles. By utilizing optical flow to quantify velocity fields, we find that micropillars disrupt collective motion and gradually decrease spatial correlation and directionality. The role of cellular junctions is examined by monitoring the dynamics of MDCK II mutants deficient in tight junction (TJ) proteins ZO1/2 and adherens junction (AJ) protein E-cadherin. TJ deficiency goes hand in hand with increased apical contractility and thereby fosters jamming, leading to generally slower, more diffusive, and spatially uncorrelated movement and an even greater reduction in collectivity in the presence of micropillars. Similarly, AJ impairment significantly decreases spatial correlation and cellular velocity but to a lesser extent. Our findings reveal that collective motion is drastically affected at a certain length scale, i.e., an interpillar distance < 80 μm, where cells resort to a more diffusive and spatially uncorrelated migration reminiscent of single-cell migration. These insights advance our understanding of how physical confinement, intercellular junctions and elevated contractility modulate collective dynamics in epithelial cells. Physical sciences/Physics/Biological physics Biological sciences/Biophysics/Motility/Cellular motility optical flow epithelial cell sheet dynamics collective migration confinement Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 30 Oct, 2025 Read the published version in Communications Physics → 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5982549","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":424477554,"identity":"23bfdd4a-ef53-4888-9d8c-2ad022124cb5","order_by":0,"name":"Andreas Janshoff","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYFCCAwwMjA0MckCWAQMDGwlajEnRwgDWkthAtBb+xsPPHv7cYZM+PyJ58wuGMhvCWiQOHDM35j2TlrvxRlqZBcO5NCKsOXDATJqx7XDuxtk5ZgZABmEd8geOf5P82XY43RCi5T9hLQYHzphJ8LYdTpCXzjF+wNh2gLAWwwNnyqR529IMN8g/K2NIOJdMWIvcjePbgA6zkZfvObz5w4cyO8JagEEGcyEDm0QCERqAEdMAoeUbGJg/EKVjFIyCUTAKRhwAABfjQFrOT4SXAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0773-2963","institution":"University of Goettingen","correspondingAuthor":true,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Janshoff","suffix":""},{"id":424477555,"identity":"20442257-9f91-4942-9e15-58030c2abe44","order_by":1,"name":"Tanmaya Sethi","email":"","orcid":"","institution":"University of Goettingen","correspondingAuthor":false,"prefix":"","firstName":"Tanmaya","middleName":"","lastName":"Sethi","suffix":""},{"id":424477556,"identity":"6317e8af-dadd-4be9-be01-58c738d8ddb2","order_by":2,"name":"Paul Nieschwitz","email":"","orcid":"","institution":"University of Goettingen","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Nieschwitz","suffix":""},{"id":424477557,"identity":"fdb93274-027f-4aab-961d-0485e3f7f4e1","order_by":3,"name":"Alf Honigmann","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Alf","middleName":"","lastName":"Honigmann","suffix":""},{"id":424477558,"identity":"ca75e1df-96f5-4c89-a606-bfae9d20de2e","order_by":4,"name":"Burkhard Geil","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Burkhard","middleName":"","lastName":"Geil","suffix":""},{"id":424477559,"identity":"7e047917-83b6-4d4f-9ed0-6a600b7258aa","order_by":5,"name":"Tabea Oswald","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tabea","middleName":"","lastName":"Oswald","suffix":""}],"badges":[],"createdAt":"2025-02-07 15:50:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5982549/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5982549/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s42005-025-02359-9","type":"published","date":"2025-10-30T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":94830051,"identity":"f9122b5b-dcfd-4d51-9659-4219811248f7","added_by":"auto","created_at":"2025-10-31 07:13:31","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1298412,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Pillarcelldynamics.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5982549/v1_covered_d4c19ab2-7b79-477b-95d5-af3db848d677.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Collective migration of epithelial cells in the\npresence of regularly spaced obstacles","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"optical flow, epithelial cell sheet dynamics, collective migration, confinement","lastPublishedDoi":"10.21203/rs.3.rs-5982549/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5982549/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Physical confinement plays a crucial role in tissue development, creating a\r\nmicroenvironment and contributing to tumorigenesis. We investigate how physical\r\nconfinement affects the collective behavior of Madin-Darby Canine Kidney\r\n(MDCK) II epithelial monolayers by introducing regularly spaced adhesive\r\nmicropillars as stiff adhesive obstacles. By utilizing optical flow to quantify\r\nvelocity fields, we find that micropillars disrupt collective motion and gradually\r\ndecrease spatial correlation and directionality. The role of cellular junctions is\r\nexamined by monitoring the dynamics of MDCK II mutants deficient in tight\r\njunction (TJ) proteins ZO1/2 and adherens junction (AJ) protein E-cadherin.\r\nTJ deficiency goes hand in hand with increased apical contractility and thereby\r\nfosters jamming, leading to generally slower, more diffusive, and spatially uncorrelated\r\nmovement and an even greater reduction in collectivity in the presence of\r\nmicropillars. Similarly, AJ impairment significantly decreases spatial correlation\r\nand cellular velocity but to a lesser extent. Our findings reveal that collective\r\nmotion is drastically affected at a certain length scale, i.e., an interpillar distance \r\n\u003c 80 μm, where cells resort to a more diffusive and spatially uncorrelated\r\nmigration reminiscent of single-cell migration. These insights advance our\r\nunderstanding of how physical confinement, intercellular junctions and elevated\r\ncontractility modulate collective dynamics in epithelial cells.","manuscriptTitle":"Collective migration of epithelial cells in the\npresence of regularly spaced obstacles","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-22 18:07:29","doi":"10.21203/rs.3.rs-5982549/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-physics","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsphys","sideBox":"Learn more about [Communications Physics](http://www.nature.com/commsphys/)","snPcode":"","submissionUrl":"","title":"Communications Physics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ba93576c-474d-4dba-9116-11cdb7560d70","owner":[],"postedDate":"April 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":45234193,"name":"Physical sciences/Physics/Biological physics"},{"id":45234194,"name":"Biological sciences/Biophysics/Motility/Cellular motility"}],"tags":[],"updatedAt":"2025-10-31T07:13:26+00:00","versionOfRecord":{"articleIdentity":"rs-5982549","link":"https://doi.org/10.1038/s42005-025-02359-9","journal":{"identity":"communications-physics","isVorOnly":false,"title":"Communications Physics"},"publishedOn":"2025-10-30 04:00:00","publishedOnDateReadable":"October 30th, 2025"},"versionCreatedAt":"2025-04-22 18:07:29","video":"","vorDoi":"10.1038/s42005-025-02359-9","vorDoiUrl":"https://doi.org/10.1038/s42005-025-02359-9","workflowStages":[]},"version":"v1","identity":"rs-5982549","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5982549","identity":"rs-5982549","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}