Intracellular Ca²⁺ Capacitors for Spatial Signaling Reprogramming: Adaptive Rectification of Metabolic Circuits

Intracellular Ca²⁺ Capacitors for Spatial Signaling Reprogramming: Adaptive Rectification of Metabolic Circuits | 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 Intracellular Ca²⁺ Capacitors for Spatial Signaling Reprogramming: Adaptive Rectification of Metabolic Circuits Haobo Pan, Pengfei Tian, Jun Gao, Yueqing Wang, Muyan Qin, Jiangtao Zhong, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9335632/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 Pathological calcium signaling arises from dysregulated intracellular Ca²⁺ microdomains, but current interventions based on channel blockade or systemic chelation cannot selectively correct spatial calcium imbalance without perturbing physiological signaling. Here we report an intracellular Ca²⁺ capacitor (iCaCap), a synthetic organelle-like platform for spatial calcium reprogramming. iCaCap is built from a mesoporous bioactive glass framework whose metastable glassy network enables rapid and reversible ion exchange: boron accelerates Ca²⁺ capture by loosening network connectivity, whereas magnesium prevents crystallization of sequestered calcium and preserves buffering reversibility. As a result, iCaCap clips pathological cytosolic Ca²⁺ spikes, limits mitochondrial Ca²⁺ overload, and restores mitochondrial bioenergetics and suppresses TRPC6–NFAT2-associated profibrotic signalling. In diabetic stress models, iCaCap restores mitochondrial homeostasis, reduces oxidative stress and limits fibrotic remodeling in vivo. In vivo, targeted delivery of iCaCap alleviates renal fibrosis and improves tissue architecture. These findings identify bioactive glass as an active intracellular ionic material, and suggest a nanomaterial-based strategy for spatial regulation of pathological calcium signalling. Biological sciences/Biotechnology/Nanobiotechnology/Nanostructures Biological sciences/Biotechnology/Nanobiotechnology/Nanoparticles Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supporting1.tif Figure S1. Effects of Ang II on Ionic Currents in NRK-52E/TRPC6 Cells. supporting2.tif Figure S2. The quantitative results of Western Blot. supporting3.tif Figure S3. H&E staining of major organs (heart, liver, spleen, lung, and kidney) after intravenous injection of icacap. supporting4.tif Figure S4. original western blot images. supporting5.tif Figure S5. original western blot images. supporting6.tif Figure S6. original western blot images. supportingnano.pdf Supporting Information Main Text 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. 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. 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-9335632","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":618803163,"identity":"456afbba-1185-4a07-ac10-9756976cc843","order_by":0,"name":"Haobo 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Here we report an intracellular Ca²⁺ capacitor (iCaCap), a synthetic organelle-like platform for spatial calcium reprogramming. iCaCap is built from a mesoporous bioactive glass framework whose metastable glassy network enables rapid and reversible ion exchange: boron accelerates Ca²⁺ capture by loosening network connectivity, whereas magnesium prevents crystallization of sequestered calcium and preserves buffering reversibility. As a result, iCaCap clips pathological cytosolic Ca²⁺ spikes, limits mitochondrial Ca²⁺ overload, and restores mitochondrial bioenergetics and suppresses TRPC6–NFAT2-associated profibrotic signalling. In diabetic stress models, iCaCap restores mitochondrial homeostasis, reduces oxidative stress and limits fibrotic remodeling in vivo. In vivo, targeted delivery of iCaCap alleviates renal fibrosis and improves tissue architecture. 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