Inducing Differential Self-Assembling Behavior in Ultrashort Peptide Hydrogelators Using Simple Metal Salts.

Controlling the self-assembly pathways can be an effective means to create complex multifunctional structures based on a single gelator design. To this direction, an ion mediated approach to control and direct supramolecular structure of the low molecular weight peptide hydrogelator would be an excellent methodology for bottom-up nanofabrication of these advanced functional materials. Our work primarily aims to understand the role of different metal ions as well as anions in modulating the self-assembly of the peptide amphiphiles. Our approach relies on rational incorporation of histidine in the peptide amphiphile, which can impart an ion responsive behavior to the hydrogels. Interestingly, the self-assembly pathway of histidine based dipeptide amphiphile was found to be largely influenced by various metal salts. A gel to sol transition occurred at physiological pH in the presence of Cu, Ni and Co ions, owing to their strong interactions with the histidine, thus shifting the gelation to pH 3.0. However, in the case of Fe and Mn, the weak interactions of histidine-metal ion can still hold the gel at physiological pH but gel strength was significantly decreased. Our studies provide a clear insight into this ion-responsive behavior across a wide pH range, which is mainly governed by the stability of a peptide-metal ion complex as per Irving-Williams series. Moreover, anions also influenced the mechanical strength as well as morphology of the nanostructures owing to their differential interaction with water as depicted in the Hofmeister series of anions. This bioinspired approach will provide an elegant strategy for accessing diverse structures, which are "out of equilibrium" and otherwise only accessible through differential molecular design. We envisage that our systematic studies on histidine-metal ion interaction can be an extremely useful methodology, which will pave a way to design and develop the stimuli responsive biomaterials.