Spider silk self-assembly via modular liquid-liquid phase separation and nanofibrillation

Ali D. Malay, Takehiro Suzuki, Takuya Katashima, Nobuaki Kono, Kazuharu Arakawa, Keiji Numata

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


Spider silk fiber rapidly assembles from spidroin protein in soluble state via an incompletely understood mechanism. Here, we present an integrated model for silk formation that incorporates the effects of multiple chemical and physical gradients on the different spidroin functional domains. Central to the process is liquid-liquid phase separation (LLPS) that occurs in response to multivalent anions such as phosphate, mediated by the carboxylterminal and repetitive domains. Acidification coupled with LLPS triggers the swift self-assembly of nanofibril networks, facilitated by dimerization of the amino-terminal domain, and leads to a liquid-to-solid phase transition. Mechanical stress applied to the fibril structures yields macroscopic fibers with hierarchical organization and enriched for β-sheet conformations. Studies using native silk gland material corroborate our findings on spidroin phase separation. Our results suggest an intriguing parallel between silk assembly and other LLPS-mediated mechanisms, such as found in intracellular membraneless organelles and protein aggregation disorders.

Original languageEnglish
Article numbereabb6030
JournalScience Advances
Issue number45
Publication statusPublished - 2020 Nov 4

ASJC Scopus subject areas

  • General


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