Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide

Abstract Although the adhesive and cohesive nature of mussel byssal proteins have long served to inspire the design of materials embodying these properties, their characteristic amino acid compositions suggest that they might also serve to inspire an unrelated material function not yet associated with this class of protein. Herein, it is demonstrated that a peptide derived from mussel foot protein‐5, a key protein in mussel adhesion, displays antibacterial properties, a yet unreported activity. This cryptic function serves as inspiration for the design of a new class of peptide‐based antibacterial adhesive hydrogels prepared via self‐assembly, which are active against drug‐resistant Gram‐positive bacteria. The gels exert two mechanisms of action, surface‐contact membrane disruption and oxidative killing affected by material‐produced H₂O₂. Detailed studies relating amino acid composition and sequence to material mechanical adhesion/cohesion and antibacterial activity affords the MIKA2 adhesive gel, a material with a superior activity that is shown to inhibit colonization of titanium implants in mice.