Cis-clustering of cadherin-23 controls the kinetics of cell-cell adhesion

Cis-clustering of cadherin-23 controls the kinetics of cell-cell adhesion | 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 Cis-clustering of cadherin-23 controls the kinetics of cell-cell adhesion Sabyasachi Rakshit, Cheerneni Srinivas, Gayathri Singaraju, Nisha Arora, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-622959/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 Cis and trans-interactions in cadherins are the foundations of cellular adhesions in multicellular organisms. While the trans-interactions mediate the intercellular attachment, the cis-interaction is presumed as reinforcement to trans. Thus, trans precedes cis has been the well-accepted model in cadherin adhesion. The stronger affinity of trans-binding over cis has been the decisive influence in the trans first model. Here we show that cadherin-23, a non-classical cadherin with an extended extracellular region, can undergo cis-clustering in solution independent of trans and phase separate as liquid droplets. Using single-molecule measurements, we decipher that weaker cis-interactions favor the cis-clustering. In-cellulo, the cis-clustering is manifested as puncta, a common feature in non-classical cadherin junctions, and accelerates the cell adhesion. The cis-clustering thus kinetically controls cell-adhesion before trans-binding. Notably, M2-macrophages predominantly express cadherin-23 and rapidly attach to circulatory tumor cells during metastatic migration. However, the relation of cis-clustering with rapid cell-cell adhesion in physiology is not yet established Biological sciences/Cell biology/Cell adhesion/Cadherins Physical sciences/Physics/Biological physics cadherin-23 cis-clustering cell-cell adhesion Full Text Additional Declarations There is NO Competing Interest. Supplementary Files FusionEventFlVideo1A.mp4 Fusion Event of droplets in fluorescence supplementaryfilenaturecommunications.pdf FusionEventBFVideo1B.mp4 Fusion event of droplets in bright field supplementaryfilenaturecommunications.pdf Supplementary file 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-622959","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":34471212,"identity":"d793f4d2-416e-445a-a581-6ee15e7b776f","order_by":0,"name":"Sabyasachi 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