Biophysical Modeling of Light-Induced Modulation in Membrane Signaling Pathways

Biophysical Modeling of Light-Induced Modulation in Membrane Signaling Pathways | 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 Research Article Biophysical Modeling of Light-Induced Modulation in Membrane Signaling Pathways mahziar Moslemipoor This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8875400/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 Light-based modulation of membrane signaling is a central tool in optogenetics and photopharmacology, enabling precise control of cellular processes. Despite rapid experimental advances, a quantitative understanding of how temporal illumination patterns interact with intrinsic receptor kinetics to shape signaling remains limited. Here, we develop a deterministic biophysical model describing membrane receptors transitioning among inactive, active, and desensitized states under external light input. Light intensity, duty cycle, and stimulation frequency are included as explicit control parameters. Steady-state analysis, stability assessment, and numerical simulations were performed to characterize responses under continuous and pulsed illumination. Pulsed stimulation outperforms continuous light by enhancing peak activation, reducing desensitization, and exploiting intrinsic recovery dynamics. Frequency-dependent analysis identifies intermediate regimes where signaling is optimized, revealing resonance-like interactions between stimulation and receptor time scales. These results demonstrate that temporal structuring of illumination, rather than total light exposure, is the key determinant of signaling efficiency , highlighting design principles for pulsed and frequency-optimized optical control. The framework is independent of specific optogenetic actuators and can be applied broadly to light-responsive systems, including photopharmacological receptors, GPCR pathways, and synthetic circuits. Overall, this work provides a predictive quantitative tool for rational design of optical stimulation protocols and advances understanding of how biophysical constraints govern membrane signaling dynamics. Biophysical modeling Membrane signaling Light-induced modulation Optogenetics Dynamical systems Full Text Additional Declarations The authors declare no competing interests. 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-8875400","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":591677873,"identity":"920954c4-c286-4816-8803-801660f457e1","order_by":0,"name":"mahziar Moslemipoor","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYFACHiT2BwaGBNK0MM4gWQszDzFadNvPHv7MU3PPbnt787HHtm12efzsDYwfPubg1mJ2Ji/BmOdYcfKcM8fSjXPbkoslew4wS87chkfLgRyDZB62hGQJiRwz6dw25sQNNxLYmHnxaTn/xuAwzz+gFvn336Qt2+qJ0HIjx7CZty3BTkKCh02ase0wMVreGDPO7UtIkOBJM5PsOXc8cWbPwWb8fjmfY/zhzbcEewn2w88kfpRVJ/azNx/88BGPFhBgAkZHYgOIxcgGJhvwqwcp+cHAYA9h/iGoeBSMglEwCkYgAABBJ1I5Aurq6AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0001-1176-2321","institution":"University of mazandaran","correspondingAuthor":true,"prefix":"","firstName":"mahziar","middleName":"","lastName":"Moslemipoor","suffix":""}],"badges":[],"createdAt":"2026-02-13 20:58:00","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8875400/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8875400/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102963660,"identity":"4a1afdbc-80f0-4fd1-bf24-d0a7c01f6e51","added_by":"auto","created_at":"2026-02-19 04:19:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":473159,"visible":true,"origin":"","legend":"","description":"","filename":"BiophysicalModelingofLightInducedModulationin.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8875400/v1_covered_9db000c5-350d-4ce9-b20e-02db7b376e3c.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eBiophysical Modeling of Light-Induced Modulation in Membrane Signaling Pathways\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of mazandaran","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Biophysical modeling, Membrane signaling, Light-induced modulation, Optogenetics, Dynamical systems","lastPublishedDoi":"10.21203/rs.3.rs-8875400/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8875400/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLight-based modulation of membrane signaling is a central tool in optogenetics and photopharmacology, enabling precise control of cellular processes. Despite rapid experimental advances, a quantitative understanding of how temporal illumination patterns interact with intrinsic receptor kinetics to shape signaling remains limited. Here, we develop a deterministic biophysical model describing membrane receptors transitioning among inactive, active, and desensitized states under external light input. Light intensity, duty cycle, and stimulation frequency are included as explicit control parameters.\u003c/p\u003e \u003cp\u003eSteady-state analysis, stability assessment, and numerical simulations were performed to characterize responses under continuous and pulsed illumination. Pulsed stimulation outperforms continuous light by enhancing peak activation, reducing desensitization, and exploiting intrinsic recovery dynamics. Frequency-dependent analysis identifies intermediate regimes where signaling is optimized, revealing resonance-like interactions between stimulation and receptor time scales.\u003c/p\u003e \u003cp\u003eThese results demonstrate that \u003cb\u003etemporal structuring of illumination, rather than total light exposure, is the key determinant of signaling efficiency\u003c/b\u003e, highlighting design principles for pulsed and frequency-optimized optical control. The framework is independent of specific optogenetic actuators and can be applied broadly to light-responsive systems, including photopharmacological receptors, GPCR pathways, and synthetic circuits. Overall, this work provides a predictive quantitative tool for rational design of optical stimulation protocols and advances understanding of how biophysical constraints govern membrane signaling dynamics.\u003c/p\u003e","manuscriptTitle":"Biophysical Modeling of Light-Induced Modulation in Membrane Signaling Pathways","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-18 05:57:16","doi":"10.21203/rs.3.rs-8875400/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b5e14def-b4e1-478b-a3d4-ada65e3a2537","owner":[],"postedDate":"February 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-18T05:57:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-18 05:57:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8875400","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8875400","identity":"rs-8875400","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}