{
  "abstract": "Cell migration is a fundamental physiological process essential from embryogenesis to cancer metastasis. It is primarily governed by the coupled mechanics of the plasma membrane (PM) and the nucleus, together with cytoskeletal dynamics. Being the largest and stiffest organelle, the nucleus is considered a rate-limiting factor in confined migration. However, nuclear positioning varies across cell types and migration modes, and the forces orchestrating its mechanical coupling with the PM are not completely understood. In recent decades, mathematical modelling has gained relevance to support cell migration research, yet models face the fundamental challenge of balancing mechanistic detail with computational efficiency. Here, we develop a dimensionless, biophysically grounded model based on geometric surface partial differential equations (GS-PDEs) for cell migration. This approach benefits from dimensional reduction—the PM and the nuclear envelope (NE) are modelled as energetic geometric membranes—and is solved using the evolving surface finite element method (ESFEM), balancing mechanistic detail with computational feasibility. The model reproduces experimentally observed migration patterns: exhaustion of lipid reservoirs and nuclear–lamina unfolding limit PM and NE surface area, blocking cell passage through constrictions; nuclear velocity peaks upon pore exit; and nuclear movement alternates between pulling and pushing regimes. Moreover, the modelling approach makes key predictions: the velocity peak upon nuclear pore exit is driven by the release of the curvature-elastic energy stored as membrane tension at the NE rear, and PM–NE mechanical coupling can hinder cell translocation, since part of the locomotion energy is invested in nuclear positioning. The model quantifies forces that are not easily experimentally accessible, including membrane tension, bending energy, osmotic pressure, PM–NE elasticity, and contact forces, offering an interpretable platform to test and propose mechanistic hypotheses on confined cell migration. Author summary: Cell migration is a fundamental physiological process, essential from embryonic development to cancer spread. In these settings, cells must traverse narrow constrictions such as pores and channels in the surrounding tissue. Being the largest and stiffest organelle, the nucleus is considered a rate-limiting factor in such confined migration. How it deforms, and how tightly it is coupled to the cell membrane, can determine whether the cell passes or remains blocked. However, nuclear positioning varies across cell types and migration modes, and the forces coupling the nucleus to the cell membrane are not easily experimentally accessible. Here, we develop a biophysically grounded mathematical model in which the cell membrane and the nuclear envelope are coupled elastic surfaces, solved numerically. The model reproduces experimentally observed migration patterns: cells become blocked when their membranes reach the limit of how much they can stretch; nuclear velocity peaks upon pore exit; and nuclear movement alternates between pulling and pushing regimes. Two mechanistic predictions emerge from the model. First, the velocity peak upon pore exit is driven by elastic energy stored as tension in the membrane at the rear of the nucleus. Second, a strong mechanical coupling between the cell membrane and the nucleus can hinder migration, since part of the locomotion energy is invested in nuclear positioning.",
  "abstract_shown": true,
  "affiliations": [
    "Université Côte d’Azur, CNRS, LJAD, Nice, France",
    "Mathematics Department, The University of British Columbia, Vancouver, Canada",
    "Department of Mathematics and Computational Sciences, University of Zimbabwe, Harare, Zimbabwe"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "David Hernandez-Aristizabal"
    },
    {
      "affs": [
        1
      ],
      "name": "Anotida Madzvamuse"
    },
    {
      "affs": [
        2
      ],
      "name": "Rachele Allena"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cttzqe3q5yzww.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014909",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014909",
  "id": "cttzqe3q5yzww",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014909",
  "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": [
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell motility/Cell migration"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cell membranes"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Cell migration"
    ],
    [
      "plos",
      "/Engineering and technology/Membrane technology/Membrane structures"
    ],
    [
      "plos",
      "/Engineering and technology/Structural engineering/Built structures/Membrane structures"
    ],
    [
      "plos",
      "/Physical sciences/Materials science/Material properties/Elasticity"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Geometry/Perimeters"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Geometry/Radii"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Classical mechanics/Damage mechanics/Deformation"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Classical mechanics/Deformation"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Classical mechanics/Pressure/Osmotic pressure"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014909&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/cttzqe3q5yzww.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:20:42Z",
      "native_id": "10.1371/journal.pcbi.1014909",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014909"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:developmental biology",
      "subfield": "developmental-biology"
    },
    {
      "field": "mathematics",
      "origin": "plos:geometry",
      "subfield": "geometry-topology"
    }
  ],
  "title": "Membrane tension and cell–nucleus mechanical coupling regulate confined cell migration",
  "title_text": "Membrane tension and cell–nucleus mechanical coupling regulate confined cell migration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:24Z",
  "url": "https://research.draconitic.com/paper/cttzqe3q5yzww",
  "venue": "PLOS Computational Biology",
  "versions": []
}