{
  "abstract": "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. Author summary: The organization of ion channels into functional clusters on cell membranes remains poorly understood. This study presents a novel computational framework that simulates dynamic channel clustering by integrating trafficking, diffusion, and channel-channel interactions. The model reveals counterintuitive relationships, including how intermediate rather than strong interactions optimize cluster formation, and demonstrates how competition between different interaction types creates complex spatial patterns in multi-channel systems. This framework enables quantitative predictions on the relationship between channel density, trafficking rates, and interaction energies collectively shape membrane organization. These insights have important implications for understanding disorders in which disrupted channel organization contributes to disease pathophysiology, offering a foundation for predicting how mutations or cellular changes affect membrane organization.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States of America",
    "Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nicolae Moise"
    },
    {
      "affs": [
        1
      ],
      "name": "Seth H. Weinberg"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/39k2z48a7c9ct.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014791",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014791",
  "id": "39k2z48a7c9ct",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014791",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Ion channel regulation and function"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Lipids"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Ion channels"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Protein transport"
    ],
    [
      "plos",
      "/Biology and life sciences/Biophysics/Ion channels"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell physiology/Membrane trafficking"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Protein transport"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cell membranes"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Neurophysiology/Ion channels"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Electrophysiology/Ion channels"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Electrophysiology/Membrane potential"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Electrophysiology/Neurophysiology/Ion channels"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Statistics/Statistical methods/Monte Carlo method"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Biophysics/Ion channels"
    ],
    [
      "plos",
      "/Research and analysis methods/Bioassays and physiological analysis/Electrophysiological techniques/Membrane electrophysiology/Single channel recording"
    ],
    [
      "plos",
      "/Research and analysis methods/Mathematical and statistical techniques/Statistical methods/Monte Carlo method"
    ]
  ],
  "openalex": "W7213461267",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014791&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/39k2z48a7c9ct.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pcbi.1014791",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014791"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:biophysics",
      "subfield": "biophysics"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "plos:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Monte Carlo modeling of the formation and organization of ion channel clustering",
  "title_text": "Monte Carlo modeling of the formation and organization of ion channel clustering",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/39k2z48a7c9ct",
  "venue": "PLOS Computational Biology",
  "versions": []
}