Bio-inspired supramolecular metallopeptide hydrogel promotes recovery from cutaneous wound

Inspired by the regulation of protein structure and function by metal ions in life, the role of metal coordination in the folding and assembly of peptides has been gradually studied. However, the construction of bioactive supramolecular metallopeptides with synergism between metal coordination and peptide self-assembly remains challenging. This paper reports a bio-inspired peptide derivative (Supra GHK (glycyl-l-histidyl-l-lysine)) bearing a natural-derived GHK tri-peptide motif, which could self-assemble into supramolecular metallopeptide hydrogel (Supra GHK-Cu) after adding Cu2+. The addition of Cu2+ prompts the allosteric effects on the folded structure of Supra GHK, resulting from the participation of atoms on the backbone of the peptide in the chelation. Cu2+ has a stronger affinity for Supra GHK by bridging two peptide molecules or interacting with one peptide molecule, as confirmed by experimental results and molecular dynamics simulation. Remarkably, due to the formation of supramolecular structures, Supra GHK-Cu possesses excellent resistance against protease degradation. Moreover, it accelerates wound healing more significantly than GHK-Cu by promoting collagen deposition, angiogenesis and cell proliferation. This work not only exemplifies a successful bio-inspired supramolecular metallopeptide hydrogel but also provides a promising alternative strategy to overcome the limitations of traditional bioactive peptides in various biomedical fields.