Myelin sheaths can act as compact temporary oxygen storage units as modeled by an electrical RC circuit model

Myelin sheaths can act as compact temporary oxygen storage units as modeled by an electrical RC circuit model | 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 Myelin sheaths can act as compact temporary oxygen storage units as modeled by an electrical RC circuit model Wouter Vervust, Katja Witschas, Luc Leybaert, An Ghysels This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4773524/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 Oxygen is a crucial component in cellular energy metabolism, particularly in the brain where neurons consume the majority of energy produced via mitochondrial oxidative phosphorylation. Phospholipid membranes have been found to store and transport oxygen efficiently in their hydrophobic core. This work investigates the kinetics of this storage, not only in a single membrane but also in membrane stacks as those found in myelinated axons in the nervous system. Using a diffusive model derived from molecular dynamics simulations, it is first demonstrate that oxygen storage within a phospholipid bilayer follows first-order kinetics. In consequence, we show how oxygen loading and unloading in a membrane is effectively modeled by an intuitive RC (resistor-capacitor) circuit analogy with a characteristic RC time constant. Next, oxygen transport through myelin, comprising multiple bilayers, could be investigated by building a ladder network of RC circuits. Both the resistance (to oxygen transport) and the capacitance (for oxygen storage) scale linearly with the number of bilayers. Moreover, the characteristic time constant for oxygen storage scales quadratically with the myelin thickness, for instance enhancing the characteristic time constant from 30 ns for one 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer to 506 μs for 200 POPC bilayers. This enhancement gives myelin a buffering role: myelin sheaths act as spatially compact oxygen containers whose slower kinetics will dampen sudden oxygen changes. Finally, oxygen transport from capillary to axonal mitochondria is modeled during increased oxygen consumption rates (OCRs) associated with neuronal activity. The model predicts that increased myelination results in longer sustainment of increased oxygen demand, supporting the idea that myelin sheaths may act as a buffer to oxygen fluctuations. The inability of considered configurations to sustain the increased OCRs for periods longer than a few hundred milliseconds hints the functional aspect of the dominant vascular response in restoring oxygen homeostasis following neuronal activation. Biological sciences/Biophysics/Computational biophysics Biological sciences/Biophysics/Nanoscale biophysics Physical sciences/Physics/Biological physics Biological sciences/Biophysics/Permeation and transport Physical sciences/Physics/Atomic and molecular physics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files myelinoxygenRCSI.pdf 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. 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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-4773524","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":334885570,"identity":"167a42a6-d88d-435a-9c4a-067e070e48b3","order_by":0,"name":"Wouter Vervust","email":"","orcid":"","institution":"Ghent University","correspondingAuthor":false,"prefix":"","firstName":"Wouter","middleName":"","lastName":"Vervust","suffix":""},{"id":334885571,"identity":"3ce31585-52ae-48d5-9956-80d204cc0e71","order_by":1,"name":"Katja Witschas","email":"","orcid":"https://orcid.org/0000-0002-0960-683X","institution":"Department of Basic Medical Sciences – Physiology group, Ghent University","correspondingAuthor":false,"prefix":"","firstName":"Katja","middleName":"","lastName":"Witschas","suffix":""},{"id":334885572,"identity":"64a0bafb-0b9c-439d-bd31-7d8b6c64e6b6","order_by":2,"name":"Luc Leybaert","email":"","orcid":"https://orcid.org/0000-0001-6452-6982","institution":"Ghent University","correspondingAuthor":false,"prefix":"","firstName":"Luc","middleName":"","lastName":"Leybaert","suffix":""},{"id":334885569,"identity":"8a25957f-c98c-43d9-b172-ea5d9abaa66e","order_by":3,"name":"An Ghysels","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYJACZhDBx8B8AMKVIFYLGwNbAkQDCVp4DIjTwj+7gfl1YVudHBv/mW+SXyru1DFINx/Aq0XizgE265lth43ZJHK3ScuceSbBIHMsAb81NxLYjHnbDiS2SfBuk5ZsOwx0WI4BXh3yEC119W38Z55JS/4Dacn/gFeLwY0E5se8bcwJbAw5bJIfG8C24HeX4Y3ENmaec4cN2yTSjK0Zjh2WbJM5ht9hcjeSD3/mKauT5+c//PDmj5rD/PzSzQ/wW8PA2CbByAZhMvMwgCKIMGD+wPAHqvsHEcpHwSgYBaNg5AEAs75BWZPfpKkAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-0015-2605","institution":"Ghent University","correspondingAuthor":true,"prefix":"","firstName":"An","middleName":"","lastName":"Ghysels","suffix":""}],"badges":[],"createdAt":"2024-07-20 14:20:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4773524/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4773524/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62806635,"identity":"6cd720f5-2a17-49b8-86c0-cbfecc41986c","added_by":"auto","created_at":"2024-08-19 17:39:34","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3048581,"visible":true,"origin":"","legend":"","description":"","filename":"myelinoxygenRCsubmitted.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4773524/v1_covered_6833c114-666f-4e00-911e-b3788ca99df0.pdf"},{"id":62270755,"identity":"e1ccb319-c53f-4e52-835d-c6340766c492","added_by":"auto","created_at":"2024-08-12 10:11:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":487413,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"myelinoxygenRCSI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4773524/v1/094217f8102804014ee4ba3f.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Myelin sheaths can act as compact temporary oxygen storage units as modeled by an electrical RC circuit model","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":"","lastPublishedDoi":"10.21203/rs.3.rs-4773524/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4773524/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Oxygen is a crucial component in cellular energy metabolism, particularly in the brain where neurons consume the majority of energy produced via mitochondrial oxidative phosphorylation. Phospholipid membranes have been found to store and transport oxygen efficiently in their hydrophobic core. This work investigates the kinetics of this storage, not only in a single membrane but also in membrane stacks as those found in myelinated axons in the nervous system. Using a diffusive model derived from molecular dynamics simulations, it is first demonstrate that oxygen storage within a phospholipid bilayer follows first-order kinetics. In consequence, we show how oxygen loading and unloading in a membrane is effectively modeled by an intuitive RC (resistor-capacitor) circuit analogy with a characteristic RC time constant. \r\nNext, oxygen transport through myelin, comprising multiple bilayers, could be investigated by building a ladder network of RC circuits. Both the resistance (to oxygen transport) and the capacitance (for oxygen storage) scale linearly with the number of bilayers. Moreover, the characteristic time constant for oxygen storage scales quadratically with the myelin thickness, for instance enhancing the characteristic time constant from 30 ns for one 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer to 506 μs for 200 POPC bilayers. This enhancement gives myelin a buffering role: myelin sheaths act as spatially compact oxygen containers whose slower kinetics will dampen sudden oxygen changes.\r\nFinally, oxygen transport from capillary to axonal mitochondria is modeled during increased oxygen consumption rates (OCRs) associated with neuronal activity. The model predicts that increased myelination results in longer sustainment of increased oxygen demand, supporting the idea that myelin sheaths may act as a buffer to oxygen fluctuations. 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