Stabilized real-time Brillouin microscopy reveals fractal organization of protein condensates in living cells

Stabilized real-time Brillouin microscopy reveals fractal organization of protein condensates in living cells | 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 Stabilized real-time Brillouin microscopy reveals fractal organization of protein condensates in living cells Claudia Testi, Emanuele Pontecorvo, Chiara Bartoli, Chiara Marzaro, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7128145/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Feb, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Mechanical alterations of protein condensates are increasingly recognized in the etiology of several neurodegenerative diseases, yet their characterization remains technically challenging. Although Brillouin microscopy could offer a promising solution, its use is hindered by instrumental instabilities demanding frequent adjustments and manual calibrations with reference materials. Here, we present an enhanced Brillouin Microscope that incorporates an electro-optic modulator, serving simultaneously as frequency reference, spectrometer calibrator, and temporal stabilizer. This integration enables robust, real-time spectral stability over multiple days in a fully automated workflow. Using this system, we quantified the mechanical properties of several protein condensates in living cells and validated our findings with FRAP measurements. The correlation between techniques reveals a fractal internal architecture of the protein condensates, providing important insights into their physical nature. Our innovative method thus offers a unique framework for distinguishing physiological from pathological condensates, paving the way for long-term, user-independent and high-precision mechanical measurements in living cells. Biological sciences/Biophysics Physical sciences/Optics and photonics/Optical techniques/Microscopy Full Text Additional Declarations There is NO Competing Interest. Supplementary Files EOMcondensatesSI.pdf Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 05 Feb, 2026 Read the published version in Nature Communications → 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-7128145","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":494634696,"identity":"d248a61b-fc39-44aa-98ff-e1b9c3badadb","order_by":0,"name":"Claudia 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