Influence of substituted aromatics on the formation and stability of β-sheet-based peptide hydrogels

Abstract

Peptide-based hydrogels are promising materials for biomedical applications including drug delivery and wound healing. However, the morphological complexity of these self-assembling materials leads to an incomplete understanding of the systems, which results in the design being often based on trial and error. In this study, the effects of phenylalanine (Phe) substitutions on the aromatic stacking of a short amphipatic β-sheet peptide hydrogelator have been investigated. Upon substituting the aromatic side chain of Phe with groups of different nature, nine hydrogels have been devised. The modifications highly altered the β-sheet organization, which resulted in fibrillar peptide hydrogels differing in morphology and material properties. The peptide gels could be categorized in three types of fibrillar networks, and the classification led to new correlations between fibril morphology, gel strength, gel transparency and network erosion rate. These findings are extremely helpful in understanding peptide hydrogels as well as predicting their properties. The presented materials are promising for further investigations toward matrices for controlled release of therapeutics.