Peptide Sequence Variations Govern Hydrogel Stiffness: Insights from a Multi‐Scale Structural Analysis of H‐FQFQFK‐NH₂ Peptide Derivatives

Throughout the past decades, amphipathic peptide-based hydrogels have proven to be promising materials for biomedical applications. Amphipathic peptides are known to adopt β-sheet configurations that self-assemble into fibers that then interact to form a hydrogel network. A fundamental understanding of how the peptide sequence alters the structural properties of the hydrogels would allow for a more rational design of novel peptides for a variety of biomedical applications in the future. Therefore, the current work investigates how changing the type of amino acid, the amphipathic pattern, and the peptide length affects the secondary structure, fiber characteristics, and stiffness of peptide-based hydrogels. Hereto, seven amphipathic peptides of different sequence and length, four of which have not been previously reported, based on and including the hexapeptide H-Phe-Gln-Phe-Gln-Phe-Lys-NH