{
  "abstract": "Background: Cerebral autoregulation stabilizes cerebral blood flow over a range of cerebral perfusion pressures, but the precise shape of the pressure-flow relationship remains debated. The classical triphasic pressure-flow relationship was recently challenged by experiments demonstrating a quadriphasic response, hypothesized to arise from vessel-size-dependent pressure-diameter responses. We tested this hypothesis and investigated whether these size-dependent responses originate from heterogeneity in smooth muscle cell (SMC) abundance, SMC behavior, or neither. Methods: We developed a computational multi-scale physics-based model of cerebral autoregulation linking SMC activity to vessel-scale diameter regulation and organ-scale blood flow. Four scenarios were evaluated: passive vessels, homogeneous SMC abundance and behavior, heterogeneous SMC abundance, and heterogeneous SMC behavior. Predicted pressure-diameter responses and pressure-flow relationships were compared across scenarios and against experimental observations. Results: In contrast to passive vessels, homogeneous SMC activation produced partial flow stabilization, highlighting the key role of SMCs in autoregulation. However, only heterogeneous SMC behavior reproduced the experimentally observed vessel-size-dependent trends in pressure-diameter responses. This scenario also showed the best agreement with the experimental organ-scale pressure-flow relationship (R-squared = 0.93, nRMSE = 5.96%). Conclusion: The model suggests that vessel-size-dependent SMC behavior underlies vessel-size-dependent pressure-diameter responses and shapes the relationship between cerebral perfusion pressure and cerebral blood flow.",
  "abstract_shown": true,
  "affiliations": [
    "KU Leuven"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "N. Demeersseman"
    },
    {
      "name": "L. Maes"
    },
    {
      "name": "B. Depreitere"
    },
    {
      "name": "N. Famaey"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/02ngmshzy82ab.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.14.751526",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751526v1.full",
  "id": "02ngmshzy82ab",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751526v1",
  "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",
      "bioengineering"
    ],
    [
      "openalex",
      "2728|Traumatic Brain Injury and Neurovascular Disturbances"
    ]
  ],
  "openalex": "W7213421819",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751526v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/02ngmshzy82ab.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:41Z",
      "native_id": "10.64898/2026.09.14.751526",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751526v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "The Role of Smooth Muscle Cell Heterogeneity in Cerebral Autoregulation: A Multi-Scale Physics-Based Modeling Study",
  "title_text": "The Role of Smooth Muscle Cell Heterogeneity in Cerebral Autoregulation: A Multi-Scale Physics-Based Modeling Study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:41Z",
  "url": "https://research.draconitic.com/paper/02ngmshzy82ab",
  "venue": "bioRxiv",
  "versions": []
}