{
  "abstract": "Glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) are platelet-activating receptors whose extracellular organization contributes to receptor association and signaling during thrombus formation, yet how alternative receptor architectures influence mechanical persistence remains unclear. We used molecular dynamics to compare a GPVI dimer based on 2GI7, a domain-swapped GPVI assembly derived from 7NMU, and a crystallographic CLEC-2 contact using the same pulling protocol and constant-force conditions. During the first 5 nm of imposed separation, reconstructed GPVI required less force and mechanical work than CLEC-2 and domain-swapped GPVI. Under constant-force loading from 400 to 600 pN, reconstructed GPVI also reached the same extension endpoint markedly earlier than the domain-swapped assembly, with passage times differing by more than an order of magnitude under several conditions. Extended pulling to approximately 10 nm produced complete loss of interreceptor heavy-atom contacts in reconstructed GPVI while local peptide and disulfide connectivity remained intact. In contrast, the domain-swapped preparation retained resistance over a larger part of the separation pathway and showed substantially greater mechanical persistence. These results show that alternative extracellular arrangements of the same receptor are not mechanically equivalent and that uncertainty in GPVI architecture can translate into large differences in force transmission and persistence under load. Such architecture-dependent persistence may influence the stability of extracellular receptor associations during thrombus formation and thereby affect the mechanical lifetime of receptor clusters under load. Author summary: Platelets form clots by recognizing molecules around them and organizing surface receptors into signaling assemblies. Two important platelet receptors, glycoprotein VI (GPVI) and CLEC-2, can experience mechanical forces as platelets interact with their surroundings during thrombus formation. GPVI has been observed in different extracellular arrangements, but it is not clear whether these structures respond differently when mechanical forces tend to pull associated receptors apart.",
  "abstract_shown": true,
  "affiliations": [
    "School of Mathematics and Statistics, Nantong University, Nantong, China.",
    "Laboratory of Biostatistics and Computational Medicine, Nantong University, Nantong, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yao Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yue Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Han Ni Soe"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhipeng Xu",
      "orcid": "0000-0001-7460-8981"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dkkj3dx493c8z.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014884",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014884",
  "id": "dkkj3dx493c8z",
  "issns": [
    "1553-7358",
    "1553-734X"
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  "language": "eng",
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  "licence_label": "CC BY",
  "licence_source": "article",
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  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2720|Platelet Disorders and Treatments"
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      "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Immune receptors"
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      "/Biology and life sciences/Biochemistry/Proteins/Intracellular receptors"
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    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cell membranes/Intracellular membranes"
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    [
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      "/Biology and life sciences/Cell biology/Signal transduction/Immune receptors"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Intracellular receptors"
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    [
      "plos",
      "/Biology and life sciences/Computational biology/Biophysical simulations"
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    [
      "plos",
      "/Biology and life sciences/Immunology/Immune system proteins/Immune receptors"
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      "/Medicine and health sciences/Immunology/Immune system proteins/Immune receptors"
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      "/Physical sciences/Chemistry/Computational chemistry/Molecular dynamics"
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      "/Physical sciences/Chemistry/Polymer chemistry/Dimers"
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      "/Physical sciences/Chemistry/Polymer chemistry/Monomers"
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      "/Physical sciences/Materials science/Materials/Oligomers/Dimers"
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      "/Physical sciences/Physics/Classical mechanics/Deformation"
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  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014884&type=printable",
  "pmcid": "PMC13690249",
  "pmid": "42868185",
  "published": "2026-10-13",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/dkkj3dx493c8z.ris",
  "sources": [
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      "first_seen": "2026-10-30T12:17:30Z",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:biophysics",
      "subfield": "biophysics"
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    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "chemistry",
      "origin": "plos:polymer chemistry",
      "subfield": "materials-polymers"
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  ],
  "title": "Distinct extracellular architectures shape mechanical persistence in GPVI and CLEC-2 receptor assemblies",
  "title_text": "Distinct extracellular architectures shape mechanical persistence in GPVI and CLEC-2 receptor assemblies",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/dkkj3dx493c8z",
  "venue": "PLOS Computational Biology",
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}