PNAS Spider Silk Paper Published
We’re excited to share our latest paper, now published in PNAS — and a strong way to close out the year with paper #10 from the lab. https://www.pnas.org/doi/10.1073/pnas.2523198122 In this study, we address a long-standing question in spider silk biology: how do soluble, intrinsically disordered silk proteins transition through liquid–liquid phase separation (LLPS) into highly ordered, β-sheet-rich fibers?By combining residue-specific solution NMR, DNP-enhanced solid-state NMR, molecular dynamics simulations, and AlphaFold3 modeling, we show that arginine–tyrosine cation–π interactions act as key molecular “stickers” that both drive phase separation and persist into the final fiber architecture. Phosphate triggers LLPS without inducing premature β-sheet formation, instead reorganizing side-chain interactions that later nucleate structural order.Importantly, we directly observe Arg–Tyr contacts in native spider silk fibers and demonstrate that arginine is partially incorporated at β-sheet interfaces, while tyrosine frequently adopts interfacial or β-turn-like conformations. This provides a mechanistic link between sequence-encoded chemistry, condensate formation, and hierarchical materials assembly in a natural structural protein.Beyond spider silk, these findings offer a general framework for understanding how weak, multivalent interactions bridge disordered and ordered states in phase-separating protein systems — with implications for biomaterials design and other biological condensates.This work was funded by the U.S. Department of Defense – Air Force Office of Scientific Research (AFOSR).Huge congratulations to the team, especially the co-first authors, Hannah Johnson and Kevin Chalek and sincere thanks to our collaborators Chris Lorenz (KCL) and Galia Debelouchina (UCSD) for making this work possible. ...
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