Modeling Radiotherapy-Induced ECM Remodeling: Implications for Cellular Migration and Tumor Growth

Modeling Radiotherapy-Induced ECM Remodeling: Implications for Cellular Migration and Tumor Growth | 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 Modeling Radiotherapy-Induced ECM Remodeling: Implications for Cellular Migration and Tumor Growth Hamed Bagheri, Jalal Kargar, Reza Laripour This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7410967/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cancer progression is governed not only by the intrinsic properties of tumour cells but also by the microenvironment through which they migrate and grow. Here we develop a hierarchical modelling framework to investigate how extracellular matrix (ECM) structure and radiotherapy together shape cell trafficking and tumour evolution. In the first part of this work we model migration in confined environments by representing a single cell as a random walker on a percolation lattice, where occupied bonds mimic ECM fibres and obstacles represent steric barriers. We then extend the model to include radiation-induced remodelling of these fibres, enabling us to quantify how dynamic changes in ECM density and orientation influence motility. In the final stage we couple the percolation-based motility to a simple tumour growth module and implement a cytotoxic effect of radiotherapy on tumour cells. Using this multi-scale model we compare treatment schedules that vary in inter-fraction time and dosage. Our results indicate that intermediate regimens—either shorter inter-fraction intervals or lower per-fraction doses—can reduce tumour burden more effectively than extreme protocols by balancing cytotoxicity with the pro-migratory side effects of ECM remodelling. These findings underscore the importance of jointly considering matrix dynamics and radiation timing when designing radiotherapy schedules. Biological sciences/Biophysics Biological sciences/Cancer Physical sciences/Mathematics and computing Health sciences/Oncology Physical sciences/Physics Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted 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-7410967","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":511881107,"identity":"38871058-4c0e-4895-8943-efe9add1df83","order_by":0,"name":"Hamed Bagheri","email":"data:image/png;base64,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","orcid":"","institution":"AJA University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Hamed","middleName":"","lastName":"Bagheri","suffix":""},{"id":511881108,"identity":"f21df032-e481-4561-b20a-1476e7e355d4","order_by":1,"name":"Jalal Kargar","email":"","orcid":"","institution":"AJA University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Jalal","middleName":"","lastName":"Kargar","suffix":""},{"id":511881109,"identity":"c07c2270-4a82-4fba-bc34-6b60b261caf9","order_by":2,"name":"Reza Laripour","email":"","orcid":"","institution":"AJA University of Meical Scinces","correspondingAuthor":false,"prefix":"","firstName":"Reza","middleName":"","lastName":"Laripour","suffix":""}],"badges":[],"createdAt":"2025-08-19 17:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7410967/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7410967/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91965238,"identity":"131269b0-fdd3-4333-9831-d11317beeea6","added_by":"auto","created_at":"2025-09-23 08:21:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1686027,"visible":true,"origin":"","legend":"","description":"","filename":"mainRadiotherapyInducedECMRemodelingEffectonCellularMigrationandTumorGrowth.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7410967/v1_covered_f0a6825b-73c9-4c51-826b-b8087bfc47ba.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Modeling Radiotherapy-Induced ECM Remodeling: Implications for Cellular Migration and Tumor Growth","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7410967/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7410967/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Cancer progression is governed not only by the intrinsic properties of tumour cells but also by the microenvironment through which they migrate and grow. Here we develop a hierarchical modelling framework to investigate how extracellular matrix (ECM) structure and radiotherapy together shape cell trafficking and tumour evolution. In the first part of this work we model migration in confined environments by representing a single cell as a random walker on a percolation lattice, where occupied bonds mimic ECM fibres and obstacles represent steric barriers. We then extend the model to include radiation-induced remodelling of these fibres, enabling us to quantify how dynamic changes in ECM density and orientation influence motility. In the final stage we couple the percolation-based motility to a simple tumour growth module and implement a cytotoxic effect of radiotherapy on tumour cells. Using this multi-scale model we compare treatment schedules that vary in inter-fraction time and dosage. 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