Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations

Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations | 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 Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations Cinzia Progida, Oda Hovet, Negar Nahali, Andrea Halaburkova, Jonas Paulsen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4175426/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Feb, 2025 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Cells sense external physical cues through complex processes involving signaling pathways, cytoskeletal dynamics, and transcriptional regulation to coordinate a cellular response. A key emerging principle underlying such mechanoresponses is the interplay between nuclear morphology, chromatin organization, and the dynamic behavior of nuclear bodies such as HP1α condensates. Here, applying super-resolution live cell imaging, we report a hitherto undescribed level of mechanoresponse triggered by cell confinement below their resting nuclear diameter, which elicits changes in the number, size and dynamics of HP1α nuclear condensates. Utilizing biophysical polymer models, we find that HP1α condensates become radially redistributed in the nucleus, dependent on the combined effect of HP1α's crosslinking activity and nuclear flattening. These insights shed new light on the complex relationship between external forces and changes in nuclear shape and chromatin organization in cell mechanoreception. Biological sciences/Cell biology/Nuclear organization Biological sciences/Cell biology/Cellular imaging/Super-resolution microscopy Biological sciences/Molecular biology/Chromatin/Chromatin remodelling Biological sciences/Biological techniques/Microscopy/Confocal microscopy Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFigures.pdf Cite Share Download PDF Status: Published Journal Publication published 25 Feb, 2025 Read the published version in Communications Biology → 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. 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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-4175426","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":288714755,"identity":"7e46ee14-6ba4-4fdc-abfd-5184ad84043b","order_by":0,"name":"Cinzia 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