Contact percolation sets flocking phase transition via chemo-mechanical feedback in heterogeneous breast cancer

Contact percolation sets flocking phase transition via chemo-mechanical feedback in heterogeneous breast cancer | 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 Contact percolation sets flocking phase transition via chemo-mechanical feedback in heterogeneous breast cancer Giorgio Scita, Leonardo Barzaghi, Chiara Guidolin, Camillo Mazzella, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6057847/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Breast cancer progression is driven by dynamic changes in tissue mechanics that promote phase transitions toward collective cell movement, immune activation, and invasion. While previous investigations primarily employed model systems of genetically identical cells, breast carcinoma consists of heterogeneous cell populations varying in genetic and mechanical traits. The complex interplay between this diversity and collective cell dynamics, affecting phase transitions and tumor progression, remains largely unexplored. Here, we interpreted our experimental data through contact percolation theory to uncover a chemo-mechanical switch underlying a phase transition via the emergence of flocking motility in heterogeneous breast cancer tissues. Using engineered mixtures of motile RAB5A-expressing cells and immotile controls, we demonstrate that interconnected system-spanning clusters of fluidized RAB5A cells induce a phenotypic switch in neighboring cells, enabling them to acquire full-scale, flocking-like motility and reprogram their transcriptional state. This transition is accompanied by the activation of pro-inflammatory gene programs. Our theoretical modelling supports a mechanism by which local cell composition drives a motility switch critical for the emergence of coordinated, system-wide movement. These findings highlight the role of mechanical heterogeneity in tumor progression and identify contact percolation as a fundamental mechanism driving dynamic tissue re-organization and immune modulation at the root of breast cancer invasion and metastasis. Biological sciences/Biophysics/Motility/Cellular motility Physical sciences/Physics/Biological physics Biological sciences/Cancer/Tumour heterogeneity Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMovie1.mp4 Movie S1 SupplementaryMovie2.mp4 Movie S2 SupplementaryMovie3.mp4 Movie S3 SupplementaryMovie4.mp4 Movie S4 SupplementaryMovie5.mp4 Movie S5 SupplementaryMovie6.mp4 Movie S6 Cite Share Download PDF Status: Under Review 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-6057847","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":430477068,"identity":"4ccfd68d-7d37-4698-9ecd-e2c607b664b4","order_by":0,"name":"Giorgio 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