{
  "abstract": "The exceptional mechanical properties of spider dragline silk originate from hierarchical spidroin self-assembly, yet mimicking this process to generate native-like structures remains challenging. Here, we report a metastable dimeric intermediate as an essential molecular factor for fibrillogenesis. Small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM) revealed a compact core stabilized by solvent-excluded \"dry interfaces\" surrounded by extended random coil regions. Within the core, a subset of the polyalanine blocks is held by side-chain packing rather than by main-chain {beta}-sheets; the majority remain exposed in the surrounding coil regions. Upon lowering the denaturant concentration, these exposed polyalanine segments pair with their counterparts at a fibril end, forming intermolecular {beta}-sheets that act as linkers and drive the stepwise end-to-end polymerization of the dimeric particles. In solution, the resulting fibrils exhibit an ordered {beta}-structure in which the polypeptide chains run parallel to the fibril axis, in contrast to amyloid-like cross-{beta}, in which the strands lie perpendicular to it; this matches key features of native silk nanofibril architecture. However, X-ray diffraction (XRD) analysis demonstrates that these native-like nanofibrils undergo an effectively irreversible transition toward amyloid-like cross-{beta} structures upon drying. Native-like fibrils are thus achievable by self-assembly, but structural control is lost during the final dehydration step. Accordingly, we propose a general principle for decoupling self-assembly from dehydration: native-like nanofibrils are formed first, then dried under conditions that restrict molecular-chain mobility (for example, mechanical constraint or immobilization on a surface), which we expect to suppress thermodynamic relaxation into cross-{beta} structures.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japa"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "H. Kajimoto"
    },
    {
      "name": "K. Yonezawa"
    },
    {
      "name": "K. S. Chan"
    },
    {
      "name": "K. Hayashi"
    },
    {
      "name": "Y. Okamoto"
    },
    {
      "name": "R. Aiba"
    },
    {
      "name": "Y. Nakatani"
    },
    {
      "name": "K. Kimura"
    },
    {
      "name": "M. Bessho"
    },
    {
      "name": "Y. Yamazaki"
    },
    {
      "name": "S. Toma-Fukai"
    },
    {
      "name": "T. Uchihashi"
    },
    {
      "name": "T. K. Sato"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Kamikubo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/30n2pdvsesdxy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.09.749980",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.749980v1.full",
  "id": "30n2pdvsesdxy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.749980v1",
  "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",
      "2502|Silk-based biomaterials and applications"
    ]
  ],
  "openalex": "W7213319286",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.749980v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/30n2pdvsesdxy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:26Z",
      "native_id": "10.64898/2026.09.09.749980",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.09.749980v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Metastable Dimeric Intermediate Drives Native-like Spidroin Fibrillogenesis, while Dehydration Promotes Cross-β Transition",
  "title_text": "Metastable Dimeric Intermediate Drives Native-like Spidroin Fibrillogenesis, while Dehydration Promotes Cross-β Transition",
  "type": "preprint",
  "updated_at": "2026-11-08T00:21:13Z",
  "url": "https://research.draconitic.com/paper/30n2pdvsesdxy",
  "venue": "bioRxiv",
  "versions": []
}