Metal Ion-Specific Modulation of Network Connectivity and Defects in Poly(ethylene glycol)–Peptide Conjugate Assemblies and Hydrogels

Self-assembling peptide-polymer conjugates offer a versatile platform to engineer nanostructures with tunable morphology and functions. Here we show that alternating phenylalanine-histidine pentapeptide units, conjugated to a short linear poly-(ethylene glycol), show pH-induced assembly into β-sheet nanofibers that act as multifunctional cross-links in the resulting hydrogels. Circular dichroism spectra demonstrate that the self-assembly is enthalpy driven at low concentrations, while rheological results suggest that the network connectivity at high concentrations is compromised by the entropic penalty of chain stretching. Metal ions (Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺) enhance secondary structures, with coordination geometry-dependent change of the global assembly. Common impacts of metal coordination include orders-of-magnitude higher network stability, an expanded linear viscoelastic region, and improved network recovery, all indicative of the fast association of metal complexes. Collectively, these results highlight the role of metal ions in tuning supramolecular packing, nanofiber morphology, and consequent hydrogel mechanics in peptide-polymer conjugate assemblies and their role in modulating structure-dynamics-property relationships for applications as stimuli-responsive biomaterials.