Anomalous Conformational Instability and Hydrogel Formation of a Cationic Class of Self-Assembling Oligopeptides

A detailed understanding of the mechanistic principles which govern peptide and protein self-assembly is of considerable biomedical and biotechnological importance. Owing to the diversity of peptide and protein sequences which have been shown to aggregate into ordered structures, the ability to self-assemble is now recognized as an inherent feature of the polypeptide backbone. It is therefore of utmost importance to elucidate the rules governing the self-assembly process. De novo designed oligopeptides, based on sequences of alternating hydrophilic and hydrophobic residues and containing complementary charge distributions, have shown the potential to self-assemble into hydrogels rich in β-sheet secondary structure. Here we present and characterize the unexpected self-assembly and hydrogel formation of AK-16, an alanine-rich oligopeptide, whose sequence does not abide by typical rules which allow for peptide self-organization. AK-16 spontaneously forms soluble, thermodynamically unstable β-sheet-rich aggregates, which can be stabilized by salt addition to yield a self-supporting macroscopic hydrogel. The AK-16 hydrogel exhibits the ability to encapsulate and slowly release a model protein. This one-charge-type system represents a novel class of self-assembling oligopeptides, in which the initial conformational instability can be exploited to tune the viscosity and physicochemical properties of the resultant hydrogel. This study provides insight for the future de novo design of self-assembling oligopeptides.