{
  "abstract": "Ca2+ is both the signal that spreads injury information through the endothelium and the trigger for phospholipid scrambling that makes a membrane procoagulant. How a blood vessel can disseminate the first without broadcasting the second is unknown. Here, we combine single-cell laser injury in endothelial monolayers with imaging of intact mesenteric vessels in vitro and intravital Ca2+ imaging in vivo. Injury generated a coherent Ca2+ wavefront that spread rapidly before progressively slowing and terminating at a reproducible boundary 197 {+/-} 7 m from the wound, engaging 50 {+/-} 8 cells. The first ring of neighboring cells exhibited a distinct response that was prevented by carbenoxolone, whereas propagation beyond this ring required extracellular ATP, purinergic receptor activation, and IP3-dependent Ca2+ release. Wavefront kinematics were consistent with ATP diffusion. In vivo, injury elicited vasoconstriction and bidirectional Ca2+ waves propagating 205 {+/-} 28 m before terminating. Remarkably, despite widespread Ca2+ elevations, phosphatidylserine (PS) externalization remained confined to the wounded cell in monolayers and intact vessels in vitro. In contrast, ionomycin-induced Ca2+ overload exposed phosphatidylserine in nearly all endothelial cells. These findings reveal an unexpected spatial uncoupling between endothelial Ca2+ signaling and phospholipid scrambling, demonstrating that Ca2+ dependent scramblase activation is subject to additional spatial regulation. The endothelium can therefore propagate injury signals across a broad field of cells while maintaining a highly localized procoagulant membrane response.",
  "abstract_shown": true,
  "affiliations": [
    "University of Vermont"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "O. Fauver"
    },
    {
      "name": "G. Hennig"
    },
    {
      "name": "A. Sackheim"
    },
    {
      "name": "B. Walters"
    },
    {
      "name": "R. Barba"
    },
    {
      "name": "R. Sonawane"
    },
    {
      "name": "C. Bidlack"
    },
    {
      "name": "D. Majumdar"
    },
    {
      "name": "M. Trebak"
    },
    {
      "name": "M. T. Nelson"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Freeman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ecfatq1v7fe12.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.760917",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760917v1.full",
  "id": "ecfatq1v7fe12",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760917v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "physiology"
    ],
    [
      "openalex",
      "2809|Ion Channels and Receptors"
    ]
  ],
  "openalex": "W7223383769",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760917v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ecfatq1v7fe12.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:20Z",
      "native_id": "10.64898/2026.10.22.760917",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760917v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Spatial uncoupling of endothelial calcium signaling from phospha-tidylserine externalization in vascular injury",
  "title_text": "Spatial uncoupling of endothelial calcium signaling from phospha-tidylserine externalization in vascular injury",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:27Z",
  "url": "https://research.draconitic.com/paper/ecfatq1v7fe12",
  "venue": "bioRxiv",
  "versions": []
}