Cross-Linking Approaches to Tuning the Mechanical Properties of Peptide π-Electron Hydrogels

Self-assembling peptides are extensively exploited as bioactive materials in applications such as regenerative medicine and drug delivery despite the fact that their relatively weak noncovalent interactions often render them susceptible to mechanical destruction and solvent erosion. Herein, we describe how covalent cross-linking enhances the mechanical stability of self-assembling it-conjugated peptide hydrogels. We designed short peptide chromophore peptide sequences displaying different reactive functional groups that can form cross-links with appropriately modified bifunctional polyethylene glycol (PEG) based small guest molecules. These peptides self-assemble into one-dimensional fibrillar networks in response to pH in the aqueous environment. The cross-linking reactions were promoted to create a secondary network locked in place by covalent bonds within the physically cross-linked (preassembled) 2z-conjugated peptide strands. Rheology measurements were used to evaluate the mechanical modifications of the network, and the chemical changes that accompany the cross-linking were further confirmed by infrared spectroscopy. Furthermore, we modified these cross-linkable it-conjugates by incorporating extracellular matrix (ECM)-derived Ile Lys Val Ala Val (IKVAV) and Arg Gly Asp (RGD) bioactive epitopes to support human neural stem and progenitor cell (hNSCs) differentiation. The hNSCs undergo differentiation into neurons on IKVAV-derived conjugates while RGD-containing peptides failed to support cell attachment. These findings provide significant insight into the biochemical and electronic properties of ir-conjugated peptide hydrogelators for creating artificial ECM to enable advanced tissue-engineering applications.