Cation-pi Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles

As an important noncovalent interaction, cation-p interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-p interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-p interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-p interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-p interaction could serve as a major driving force to trigger peptide folding, resultant beta-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-p interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.