Light-sheet photonic force optical coherence elastography for high-throughput quantitative 3D micromechanical imaging

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Abstract Microscale mechanical properties of the extracellular matrix (ECM) and dynamic cell-ECM interactions play an important role in pathophysiological processes, including the onset, progression, and attenuation of disease. The ability to quantitatively image cell-mediated micromechanical dynamics of the ECM in physiologically relevant 3D engineered cellular systems can significantly enhance the clinical translational potential of fundamental discoveries in the rapidly growing field of mechanobiology. However, it remains a challenge for current mechanical characterization methods to combine quantitative 3D imaging of ECM mechanics with cellular-scale resolution and dynamic monitoring of cell‑mediated changes to pericellular viscoelasticity. Here, we present light-sheet photonic force optical coherence elastography (LS-pfOCE) to address this challenge by leveraging a light-sheet for parallelized, non-invasive, and localized mechanical loading. We demonstrate the capabilities of LS-pfOCE by imaging the micromechanical heterogeneity of fibrous 3D collagen matrices and perform a live-cell study to image micromechanical heterogeneity induced by NIH-3T3 cells seeded in 3D fibrin constructs. We also show that LS-pfOCE is able to quantify temporal variations in pericellular viscoelasticity in response to drug-induced altered cellular activity. By providing access to 4D spatiotemporal variations in the micromechanical properties of 3D biopolymer constructs and engineered cellular systems, LS‑pfOCE has the potential to drive new discoveries in mechanobiology and contribute to the development of novel biomechanics-based clinical diagnostics and therapies.
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Light-sheet photonic force optical coherence elastography for high-throughput quantitative 3D micromechanical imaging | 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 Light-sheet photonic force optical coherence elastography for high-throughput quantitative 3D micromechanical imaging Yuechuan Lin, Nichaluk Leartprapun, Justin Luo, Steven Adie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-900142/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Jun, 2022 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Microscale mechanical properties of the extracellular matrix (ECM) and dynamic cell-ECM interactions play an important role in pathophysiological processes, including the onset, progression, and attenuation of disease. The ability to quantitatively image cell-mediated micromechanical dynamics of the ECM in physiologically relevant 3D engineered cellular systems can significantly enhance the clinical translational potential of fundamental discoveries in the rapidly growing field of mechanobiology. However, it remains a challenge for current mechanical characterization methods to combine quantitative 3D imaging of ECM mechanics with cellular-scale resolution and dynamic monitoring of cell‑mediated changes to pericellular viscoelasticity. Here, we present light-sheet photonic force optical coherence elastography (LS-pfOCE) to address this challenge by leveraging a light-sheet for parallelized, non-invasive, and localized mechanical loading. We demonstrate the capabilities of LS-pfOCE by imaging the micromechanical heterogeneity of fibrous 3D collagen matrices and perform a live-cell study to image micromechanical heterogeneity induced by NIH-3T3 cells seeded in 3D fibrin constructs. We also show that LS-pfOCE is able to quantify temporal variations in pericellular viscoelasticity in response to drug-induced altered cellular activity. By providing access to 4D spatiotemporal variations in the micromechanical properties of 3D biopolymer constructs and engineered cellular systems, LS‑pfOCE has the potential to drive new discoveries in mechanobiology and contribute to the development of novel biomechanics-based clinical diagnostics and therapies. Biophysics Photonics/optics extracellular matrix LS-pfOCE quantitative 3D imaging Full Text Additional Declarations Yes there is potential Competing Interest. The authors declare the following competing interests: N.L. and S.G.A. are listed as inventors on U.S. Patent No. US10072920B2 and US10197379B2. Y.L., N.L., and S.G.A are listed as inventors on U.S. Provisional Patent Application No. 62/968,961. Supplementary Files LSpfOCENatCommfullSupplementaryVideo1submitted.mp4 Live-cell LS-pfOCE measurement under normal condition LSpfOCENatCommfullSupplementaryVideo2submitted.mp4 Live-cell LS-pfOCE measurement after Cytochalasin D treatment LSpfOCENatCommSupplementary.docx Cite Share Download PDF Status: Published Journal Publication published 16 Jun, 2022 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. 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. 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