{
  "abstract": "Acinar-to-ductal metaplasia (ADM) is an early pancreatic cell-state transition associated with injury, inflammation, and progression toward pancreatic intraepithelial neoplasia (PanIN). Although genetic and inflammatory drivers of ADM are well established, the contribution of extracellular-matrix mechanics is difficult to isolate because tissue stiffening is accompanied by changes in matrix composition and soluble signaling. Here, we describe a two-dimensional polyacrylamide (PAA) hydrogel platform that independently varies substrate stiffness and adhesive ligand presentation for murine pancreatic acinar 266-6 cells. Hydrogels approximate soft pancreatic tissue (0.50 kPa), a transitional mechanical condition (4.48 kPa), and fibrotic tissue (18.29 kPa). RGD provides a conventional adhesive cue relevant across healthy-to-fibrotic extracellular-matrix states, whereas incorporation of laminin-derived isoleucine-lysine-valine-alanine-valine (IKVAV) creates a more basement-membrane-like environment consistent with preservation of acinar identity. The platform was also adapted to include gelatin, a collagen-derived protein used here to model a more collagen-rich fibrotic matrix context. Peptide coupling is calibrated using fluorescently labeled RGD, and responses after 3 days are assessed by morphology, alpha-amylase 2 (AMY2), Yes-associated protein (YAP) nuclear-to-cytoplasmic localization, and sex-determining region Y-box transcription factor 9 (SOX9). Increasing stiffness increased nuclear YAP localization and reduced AMY2 expression. IKVAV-containing conditions supported greater attachment on softer matrices and partially preserved acinar-like phenotype on stiff gels despite elevated nuclear YAP. Across all ligand conditions, increasing stiffness reduced roundness and geometric regularity/solidity and increased aspect ratio; on gelatin-modified hydrogels, these phenotypic changes corresponded to increased cell-area-normalized SOX9 fluorescence. Together, these readouts identify a stiffness-dependent shift from an acinar-associated state toward an ADM-associated ductal phenotype, while ligand context modulates how this mechanical response is expressed. This protocol provides a controllable, adaptable system for separating mechanical and biochemical extracellular-matrix inputs during pancreatic phenotypic plasticity.",
  "abstract_shown": true,
  "affiliations": [
    "University of Glasgow"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "S. S. Ayyalasomayajula"
    },
    {
      "name": "J. P. Morton"
    },
    {
      "name": "C. C. Berry"
    },
    {
      "affs": [
        0
      ],
      "name": "M. J. Walker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9mzf3m42gbcar.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.15.759386",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759386v1.full",
  "id": "9mzf3m42gbcar",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759386v1",
  "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",
      "cancer biology"
    ],
    [
      "openalex",
      "1307|Cellular Mechanics and Interactions"
    ]
  ],
  "openalex": "W7222553463",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759386v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9mzf3m42gbcar.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:09Z",
      "native_id": "10.64898/2026.10.15.759386",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759386v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Engineering tunable synthetic fibrotic niches to model acinar-to-ductal metaplasia in 2D pancreatic culture systems",
  "title_text": "Engineering tunable synthetic fibrotic niches to model acinar-to-ductal metaplasia in 2D pancreatic culture systems",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:09Z",
  "url": "https://research.draconitic.com/paper/9mzf3m42gbcar",
  "venue": "bioRxiv",
  "versions": []
}