What is it about?
Spider silk starts as a dense liquid protein “dope” inside the spider before transforming into one of nature’s toughest fibers. We show that this transformation begins when silk proteins undergo liquid–liquid phase separation, forming protein-rich droplets. Using advanced NMR spectroscopy, molecular simulations, and AI-based structure prediction, we identify specific interactions between arginine and tyrosine amino acids that act like molecular connectors. These interactions help proteins condense while remaining flexible, and later persist as the proteins lock into ordered β-sheet structures in the final fiber. Our results reveal how subtle, sequence-encoded chemical interactions link liquid condensation to solid fiber formation.
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Why is it important?
Spider silk is a benchmark for strong, lightweight, and sustainable materials, but reproducing its properties synthetically has been difficult. One major challenge is understanding how soluble silk proteins transition into solid fibers without premature aggregation. This work identifies a specific molecular mechanism—arginine–tyrosine cation–π interactions—that bridges this gap. By directly linking phase separation to structural ordering at the amino-acid level, our findings explain how spiders control fiber assembly with precision. More broadly, the results provide general design rules for how intrinsically disordered proteins use weak interactions to build functional materials, with implications for biomaterials, soft matter, and protein phase separation in biology.
Perspectives
These insights open new directions for designing synthetic silk-like fibers that better mimic natural spinning pathways. By tuning residue-level interactions rather than forcing full protein folding, it may be possible to create materials that assemble hierarchically with improved toughness and processability. Beyond silk, the framework developed here can be applied to other biological materials that rely on phase separation, such as elastin, nacre, and protein condensates inside cells. Future work will explore how additional residues and environmental cues—such as flow and pH—work together with phase separation to control large-scale material properties.
Gregory Holland
San Diego State University
Read the Original
This page is a summary of: Arg–Tyr cation–π interactions drive phase separation and β-sheet assembly in native spider dragline silk, Proceedings of the National Academy of Sciences, December 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2523198122.
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