A Short Peptide Hydrogel with High Stiffness Induced by 3₁₀-Helices to β-Sheet Transition in Water

Biological gels generally require polymeric chains that produce long-lived physical entanglements. Low molecular weight colloids offer an alternative to macromolecular gels, but often require ad-hoc synthetic procedures. Here, a short biomimetic peptide composed of eight amino acid residues derived from squid sucker ring teeth proteins is demonstrated to form hydrogel in water without any cross-linking agent or chemical modification and exhibits a stiffness on par with the stiffest peptide hydrogels. Combining solution and solid-state NMR, circular dichroism, infrared spectroscopy, and X-ray scattering, the peptide is shown to form a supramolecular, semiflexible gel assembled from unusual right-handed 3₁₀-helices stabilized in solution by π-π stacking. During gelation, the 3₁₀-helices undergo conformational transition into antiparallel β-sheets with formation of new interpeptide hydrophobic interactions, and molecular dynamic simulations corroborate stabilization by cross β-sheet oligomerization. The current study broadens the range of secondary structures available to create supramolecular hydrogels, and introduces 3₁₀-helices as transient building blocks for gelation via a 3₁₀-to-β-sheet conformational transition.