Cooperative Metal Ion Coordination to the Short Self‐Assembling Peptide Promotes Hydrogelation and Cellular Proliferation

Abstract Noncovalent interactions among short peptides and proteins lead to their molecular self‐assembly into supramolecular packaging, which provides the fundamental basis of life. These biomolecular assemblies are highly susceptible to the environmental conditions, including temperature, light, pH, and ionic concentration, and thus inspiring the fabrication of a new class of stimuli‐responsive biomaterials. Here, for the first time the cooperative effect of the divalent metal ions to promote hydrogelation in the short collagen inspired self‐assembling peptide for developing advanced biomaterials is reported. Introduction of the biologically relevant metal ions (Ca2+/Mg2+) to the peptide surpasses its limitation to self‐assemble into a multiscale structure at physiological pH. In particular, in presence of metal ions, the negatively charged peptide shows a distinct shift in its equilibrium point of gelation and demonstrates conversion from sol to gel and thus enabling the scope of fabricating an advanced biomaterial for controlling cellular behavior. Interestingly, tunable mechanical strength and improved cellular response are observed within ion‐coordinated peptide hydrogels compared to the peptide gelator. Microscopic analyses, rheological assessment, and biological studies establish the importance of utilizing a novel strategy by simply using metal ions to modulate the physical and biological attributes of collagen inspired peptide (CIPs) to construct next‐generation biomaterials.