Force-Activated Slip-Catch-Slip Bonds Stabilize Virus Interactions

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Force-Activated Slip-Catch-Slip Bonds Stabilize Virus Interactions | 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 Force-Activated Slip-Catch-Slip Bonds Stabilize Virus Interactions Manuel Göz, Daniel Korte, Jannik Wiehenkamp, Yasan Karam, Volker Walhorn, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8797158/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 Viral adhesion often relies on dynamic molecular interactions that adapt to mechanical stress. Here, we report that SARS-CoV-2 spike proteins form catch bonds with the human ACE2 receptor, whereby moderate tensile forces enhance bond lifetimes before yielding at higher loads. Using single-molecule atomic force spectroscopy, we quantitatively resolved these nonmonotonic force–lifetime relationships for Alpha, Delta, and Omicron variants. The catch-bond regime between 15–35 pN reveals a mechanically tuned adhesion mechanism that may stabilize viral attachment in the dynamic respiratory environment. A two-state-two-pathway kinetic model reproduces the observed slip–catch–slip behavior, demonstrating that mechanical force can transiently strengthen viral receptor binding. These findings uncover a previously unrecognized biophysical strategy of SARS-CoV-2 that may influence infectivity and transmission. Physical sciences/Physics Physical sciences/Physics/Biological physics SARS-CoV-2 ACE2 AFM-SMFS Full Text Additional Declarations There is NO Competing Interest. Supplementary Files ExtendedDataFigure1.jpg Extended Data Figure EDF 1 Table1.pdf Table 1 ExtendedDataTable2.jpg Extended Data Table EDT 2 ExtendedDataTable3.jpg Extended Data Table EDT 3 ExtendedDataTable1.jpg Extended Data Table EDT 1 ExtendedDataFigure2.jpg Extended Data Figure EDF 2 ExtendedDataFigure3.jpg Extended Data Figure EDF 3 ExtendedData.pdf Extended Data ExtendedDataFigure4.jpg Extended Data Figure EDF 4 SupplementaryInformation.pdf Supplementary Information 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. 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