Collagen-Inspired Helical Peptide Coassembly Forms a Rigid Hydrogel with Twisted Polyproline II Architecture
Moumita Ghosh, Santu Bera, Sarah Schiffmann, Linda J. W. Shimon, Lihi Adler‐Abramovich
Abstract
Collagen, the most abundant protein in mammals, possesses notable cohesion and elasticity properties and efficiently induces tissue regeneration. The Gly-Pro-Hyp canonical tripeptide repeating unit of the collagen superhelix has been well-characterized. However, to date, the shortest tripeptide repeat demonstrated to attain a helical conformation contained 3-10 peptide repeats. Here, taking a minimalistic approach, we studied a single repeating unit of collagen in its protected form, Fmoc-Gly-Pro-Hyp. The peptide formed single crystals displaying left-handed polyproline II superhelical packing, as in the native collagen single strand. The crystalline assemblies also display head-to-tail H-bond interactions and an "aromatic zipper" arrangement at the molecular interface. The coassembly of this tripeptide, with Fmoc-Phe-Phe, a well-studied dipeptide hydrogelator, produced twisted helical fibrils with a polyproline II conformation and improved hydrogel mechanical rigidity. The design of these peptides illustrates the possibility to assemble superhelical nanostructures from minimal collagen-inspired peptides with their potential use as functional motifs to introduce a polyproline II conformation into hybrid hydrogel assemblies.