{
  "abstract": "Talin is a central mechanosensitive adaptor that links integrins to the actin cytoskeleton and converts mechanical force into biochemical signals. Vertebrates express two highly homologous talin isoforms, talin-1 and talin-2, yet the molecular basis for their nonredundant functions remains poorly understood. Here, we investigate how isoform-specific sequence differences alter the mechanical response and ligand-binding capabilities of the talin rod. Using single-molecule force spectroscopy and biochemical binding assays, we show that talin-2 preserves the overall mechanical architecture of talin-1 but exhibits distinct mechanical responses in key rod regions. Talin-2 R7-R9 exhibits a previously unobserved three-domain cooperative unfolding pathway, while an alternative sequential pathway reveals early unfolding of R9 at substantially lower force than in talin-1. Strikingly, talin-2 R4-R6 has acquired two additional mechanically regulated interactions: a previously unrecognized vinculin-binding site in R5 and an A-kinase anchoring protein (AKAP) region within R5-R6 that recruits protein kinase A (PKA). Together with the conserved R9 AKAP site, this establishes two spatially separated, mechanically regulated PKA-anchoring regions within the talin-2 scaffold. These findings establish that isoform-specific sequence divergence not only reshapes the mechanical response of the talin scaffold but also expands its repertoire of force-regulated interactions, providing a mechanism for the assembly of different structural and signaling complexes in an isoform-dependent manner.",
  "abstract_shown": true,
  "affiliations": [
    "Mechanobiology Institute, Department of Physics, National University of Singapore"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Y. Guo"
    },
    {
      "name": "D. Guttula"
    },
    {
      "name": "M. Yao"
    },
    {
      "name": "D. M. Cooper"
    },
    {
      "name": "N. Ball"
    },
    {
      "name": "B. Klapholz"
    },
    {
      "name": "A. Price"
    },
    {
      "name": "A. Howe"
    },
    {
      "name": "B. T. Goult"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Yan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/31e4kejhxg8xr.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.05.764451",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764451v1.full",
  "id": "31e4kejhxg8xr",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764451v1",
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764451v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/31e4kejhxg8xr.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:02Z",
      "native_id": "10.64898/2026.11.05.764451",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764451v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Highly conserved talin isoforms encode distinct mechanical responses and ligand-binding capabilities",
  "title_text": "Highly conserved talin isoforms encode distinct mechanical responses and ligand-binding capabilities",
  "type": "preprint",
  "updated_at": "2026-11-08T00:21:00Z",
  "url": "https://research.draconitic.com/paper/31e4kejhxg8xr",
  "venue": "bioRxiv",
  "versions": []
}