Modular Tunable α‐Helical Peptide Hydrogels for Neuronal Cells

Abstract The assembly of synthetic modules into user‐defined hydrogels for cell culture and clinical applications carries significant advantages over naturally derived materials. Modularity is exploited in synthetic‐polymer‐based hydrogels to alter their physical properties, and spatiotemporally incorporate signaling peptides and growth factors. By contrast, the design of self‐assembling peptide hydrogels has focused largely on assessing cellular responses to unmodified hydrogels and introducing small cell‐adhesive ligands. In short, the modularity of peptide hydrogels is yet to be fully exploited. Previously, hydrogelating self‐assembling fibers (hSAFs) are reported in which two de novo designed α‐helical peptides form gels when mixed. Here, rational peptide design and engineering are used to alter the elastic properties of these hydrogels, to introduce adhesion peptides and growth factors, and to spatially pattern proteins within them. Analysis of the viability and morphology of primary rat neurons cultured on these hydrogels indicates that the modularity of the hSAF system provides a flexible platform for manipulating cell behavior, with potential future applications for modeling natural systems in vitro and regenerative medicine in vivo.