{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:13:33Z","timestamp":1790100813140,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014791","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL165751"],"award-info":[{"award-number":["R01HL165751"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25CDA1436439"],"award-info":[{"award-number":["25CDA1436439"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The spatial organization of ion channels on cell membranes critically influences many key physiological processes, such as cardiac and neuronal excitability and cellular signaling, yet the mechanisms governing channel clustering remain poorly understood. In this study, we present a stochastic computational framework that models the dynamic organization of ion channels through Monte Carlo simulations incorporating membrane insertion, removal, channel-channel interactions, and diffusion processes. Our model reveals several fundamental principles of membrane domain formation. In single-channel systems, we demonstrate a biphasic relationship between interaction energy and cluster size, with optimal clustering occurring at intermediate interaction strengths, suggesting that excessively strong interactions can impede cluster growth by restricting channel mobility. In two-channel systems, we find that the interplay between homotypic and heterotypic interactions determines whether channels form mixed or segregated clusters, with asymmetric clustering behaviors emerging when homotypic interaction strengths differ between channel types. Simulations of three-channel systems demonstrate emergent organizational principles leading to hierarchical clustering patterns and specialized domain formation. These findings generate testable predictions about how channel density, trafficking dynamics, and interaction energies collectively alter ion channel spatial organization, in the setting of both physiological function and pathophysiological conditions.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014791","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:39:31Z","timestamp":1789666771000},"page":"e1014791","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monte Carlo modeling of the formation and organization of ion channel clustering"],"prefix":"10.1371","volume":"22","author":[{"given":"Nicolae","family":"Moise","sequence":"first","affiliation":[{"name":"The Ohio State University","place":["Columbus, Ohio, United States of America"],"department":["Department of Biomedical Engineering"]},{"name":"The Ohio State University Wexner Medical Center","place":["Columbus, 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