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

Abstract

Abstract 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.

Keywords

• β‐sheet transition
• molecular dynamics (MD) simulations
• NMR spectroscopy
• peptide hydrogels
• suckerin