High Entropy-Production Zone (HEZ) and Marangoni Effect-Driven Convection: A Hypothesis for Corneal Stromal Dynamics

High Entropy-Production Zone (HEZ) and Marangoni Effect-Driven Convection: A Hypothesis for Corneal Stromal Dynamics | 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 High Entropy-Production Zone (HEZ) and Marangoni Effect-Driven Convection: A Hypothesis for Corneal Stromal Dynamics Yasushi Sonoda This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7456650/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract The cornea is a metabolically active, transparent tissue considered to be a nonequilibrium open biological system that must continuously dissipate internally generated entropy to maintain its highly ordered structure and optical transparency. Here, we present a biophysical modeling framework integrating thermodynamics, fluid dynamics, and computational simulations to explain corneal homeostasis. We propose the existence of a functional High Entropy-Production Zone (HEZ) within the anterior stroma, where sustained metabolic activity establishes persistent thermal and solute gradients. These gradients are hypothesized to drive Marangoni effects, particularly solutal Marangoni forces, promoting efficient entropy dissipation toward the anterior chamber. Based on thermodynamic principles, we first hypothesized the existence of a High Entropy-Production Zone (HEZ) within the anterior stroma, predicting that Marangoni-driven convection would emerge. Using AMR-DNS-based conceptual simulations, we then tested these predictions against the experimental benchmark of Inoue et al., finding strong concordance. These results support the physiological plausibility of HEZ and Marangoni-driven convection and are thought to indicate the mechanisms of entropy dissipation and the dual-engine hypothesis within corneal tissue. In this study, we introduce the entropy balance equation (ΔS in – ΔS out ≤ 0) as a fundamental principle for integratively understanding stromal metabolism, endothelial transport, and thermodynamic stability. Disruption of this entropy balance may underlie various corneal pathologies, including keratoconus, corneal edema, and graft rejection. Furthermore, this framework represents an interdisciplinary approach that bridges experimental findings, computational modeling, and clinical applications, providing new perspectives on corneal physiology and disease mechanisms. Biophysics Ophthalmology cornea entropy dissipation High Entropy-production Zone (HEZ) Marangoni effect AMR‑DNS endothelial pump biophysics ophthalmology Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Supplementaryfiles.zip Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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-7456650","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":510876041,"identity":"e441792d-0216-4c40-a4cd-4b0bac56aed5","order_by":0,"name":"Yasushi Sonoda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYLACHgjFxpBQAaSYmRtI0XIGpIWRFC2MbSCagBb59t6DD97UHJaXn5H+7MHDebXR/O1ALT8qtuHUYnDmXLLhnGOHDTfcyDE3SNx2PHfGYcYGxp4zt3Frkcgxk+ZhO8y4QSKHTSJx27HcBqAWZsY23FrkZ4C0/DtsPx/oMInEOcdy5xPSwnADqIW37XBiw40EM4nEhprcDYS0GJw5Y2w4ty89ecOZN2YSCccO5G4EajmIzy/y7T2GD958s7ad357+TPJHTV3uvPOHDz74UYHHYRDQDGMcBpMHCKkHgjoMxigYBaNgFIwCOAAAJQVer+9M8tUAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0009-6784-0323","institution":"Mejiro Dori Clinic","correspondingAuthor":true,"prefix":"","firstName":"Yasushi","middleName":"","lastName":"Sonoda","suffix":""}],"badges":[],"createdAt":"2025-08-25 19:43:30","currentVersionCode":2,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7456650/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-7456650/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90925479,"identity":"010739a1-5870-4457-81fd-63a2374226b8","added_by":"auto","created_at":"2025-09-09 15:26:38","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":733718,"visible":true,"origin":"","legend":"","description":"","filename":"NewVersion20250909HighEntropyProductionZoneHEZandMarangoniEffectDrivenConvectionAHypothesisforCornealStromalDynamics.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7456650/v2_covered_e7e90347-76a6-4a9f-93e1-44ad2bae7025.pdf"},{"id":90922142,"identity":"71cabfd6-b98f-4c6a-8d21-9c96d2cb39e2","added_by":"auto","created_at":"2025-09-09 15:02:36","extension":"zip","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":50670,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfiles.zip","url":"https://assets-eu.researchsquare.com/files/rs-7456650/v2/95ba5aad69de3648d6e122fa.zip"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eHigh Entropy-Production Zone (HEZ) and Marangoni Effect-Driven Convection: A Hypothesis for Corneal Stromal Dynamics\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","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":"cornea, entropy dissipation, High Entropy-production Zone (HEZ), Marangoni effect, AMR‑DNS, endothelial pump, biophysics, ophthalmology","lastPublishedDoi":"10.21203/rs.3.rs-7456650/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7456650/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe cornea is a metabolically active, transparent tissue considered to be a nonequilibrium open biological system that must continuously dissipate internally generated entropy to maintain its highly ordered structure and optical transparency. 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