Liquid‒liquid phase separation of spider silk proteins

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Zeußel, Lisa ; Bargel, Hendrik ; Holland, Gregory P. ; Scheibel, Thomas:
Liquid‒liquid phase separation of spider silk proteins.
In: Polymer Journal. Bd. 57 (2025) . - S. 831-843.
ISSN 1349-0540
DOI: https://doi.org/10.1038/s41428-025-01039-3

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Abstract

Liquid‒liquid phase separation (LLPS) is a phenomenon relevant in the multicomponent settings of many biological processes, including compartmentation, pathological conditions such as Alzheimer’s disease, and protein assembly. LLPS also plays a key role in spider silk fiber formation. Many spider silk fibers display properties such as elasticity in combination with high mechanical strength, which result in an outstanding toughness exceeding that of steel or Kevlar. A thorough understanding of the natural silk spinning process is thus vital for translation to artificial spinning techniques to achieve biomimetic fibers with properties superior to those of other fibrous materials. This focus review summarizes the milestones of research on spider silk assembly, starting from two initial theories, i.e., the liquid crystal theory and the micelle theory, followed by evidence for the importance of LLPS in this process. Ex vivo studies and experiments utilizing recombinant spider silk proteins have highlighted the importance of LLPS during spider silk assembly. Here, we provide a consolidated view of the previously separate theories as a concerted, transitional concept, and describe practical implications showcasing the importance of this unifying concept for technical silk spinning.