Intermediate States Enable Keratin-like α-To-β Transformations in Strain-Responsive Synthetic Polypeptides

• DOI: 10.1021/jacs.5c02148
• Publication Date: 2025-04-22T19:20:41Z
• Authors: Tianjian Yang; Jianan Mao; Tianrui Xue; Siyu Wu; Ruipeng Li; Yingying Chen; Abrar A. Sitab; Jianjun Cheng; Yao Lin
• Keywords: Strain (injury)

Nature's fibrous proteins, such as α-keratin, achieve remarkable mechanical properties by undergoing strain-induced α-to-β conformational transitions. Inspired these materials, we report a strategy for designing synthetic polypeptides that undergo similar transformations at elevated temperatures far exceeding keratin's operational range. By employing helix-confined ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) initiated short poly(γ-benzyl-l-glutamate) (PBLG) precursor, synthesized poly(O-benzyl-l-serine) (PBLS) chains adopt an α-helical structure yet transition into β-sheets upon heating. Compression molding carefully chosen drives PBLS segments α-β intermediate state, characterized relaxed intrachain hydrogen bonds and hexagonal packing arrangement. Under strain, states convert in situ β-sheets, producing significant strain-hardening well below the spontaneous temperature threshold. This approach extends to bearing different side chains, poly(S-benzyl-l-cysteine), demonstrating robust reinforcement across wide window up ∼ 200 °C. In synchrotron X-ray analysis confirms chain alignment, β-sheet formation, domain growth occur stepwise during deformation. harnessing supramolecular cooperativity conferred compression-molded films, our method provides versatile platform developing next-generation polypeptide materials with tunable resilience responsiveness─surpassing limitations natural proteins enabling potential applications demanding broad-temperature adaptability.