{
  "abstract": "Cerebral cavernous malformations (CCM) are vascular lesions characterized by impaired endothelial integrity and altered cell-cell and cell-matrix interactions. While endothelial contractility and tractions have been implicated in CCM, how these forces are transmitted and coordinated across adhesion systems remains unknown. Here, we combined genetically encoded FRET-based molecular tension sensors of vinculin and VE-cadherin with quantitative analysis of adhesion organization to dissect this force balance in CCM2-deficient endothelial monolayers. We found that CCM2 loss redistributes molecular forces, partially through ROCK-dependent contractility, across endothelial adhesions, shifting mechanical engagement from cell-cell junctions toward the cell-matrix interface. Matrix stiffness further amplifies this imbalance, as healthy endothelial cells maintain the balance between cell-cell and cell-matrix adhesions by reinforcing both in response to stiffening, whereas CCM2-deficient cells preferentially reinforce the cell-matrix interface. These findings suggest that CCM-associated matrix remodeling could reinforce an already altered mechanical state, establishing a potential feed-forward interaction between endothelial force transmission and the extracellular environment. More broadly, our results identify the CCM complex as a molecular hub controlling force balance in response to the cell mechanical environment and establish a combined tension sensing and morphology-based imaging platform for studying adhesion mechanobiology.",
  "abstract_shown": true,
  "affiliations": [
    "KULeuven"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "S. vorsselmans"
    },
    {
      "name": "S. Aytekin"
    },
    {
      "name": "C. Oddou"
    },
    {
      "name": "T. Manicom Ramsamy"
    },
    {
      "name": "E. Faurobert"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Rocha"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f76y2d2v6vpex.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.757835",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757835v1.full",
  "id": "f76y2d2v6vpex",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757835v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1307|Cellular Mechanics and Interactions"
    ]
  ],
  "openalex": "W7222573649",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757835v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f76y2d2v6vpex.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:12Z",
      "native_id": "10.64898/2026.10.09.757835",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757835v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Letting go to hold on: loss of CCM2 disrupts endothelial force balance in cerebral cavernous malformations",
  "title_text": "Letting go to hold on: loss of CCM2 disrupts endothelial force balance in cerebral cavernous malformations",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:12Z",
  "url": "https://research.draconitic.com/paper/f76y2d2v6vpex",
  "venue": "bioRxiv",
  "versions": []
}