Metal Ion–Induced Cross-Linking in Mucin-Inspired Peptide Hydrogels

Abstract

Mucus is the biological hydrogel that lines the mucosal surfaces of mammals and acts as a protective barrier. Its main proteinaceous component is mucin, the high molecular weight, degree of glycosylation, and hardly uniquely defined nature of which hamper precise structures/property investigations based on biological samples. In contrast, chemically precisely defined peptide model systems inspired by such natural glycoproteins represent synthetically readily obtainable tools with excellent properties for both fundamental research and biomedical applications. Herein, we report the design and characterization of a library of histidine- and monosaccharide-containing coiled coil peptides that form hydrogels to different degrees in the presence of divalent metal ions Cu²⁺, Zn²⁺, Ca²⁺, and Fe²⁺. Using rheology, circular dichroism, and transmission electron microscopy, we determined the viscoelastic properties and global structures of these glycopeptide materials. This study reflects the interplay between glycan identity, histidine position, and divalent metal ion on the mechanical strength of these hydrogels.