A versatile cyclic dipeptide hydrogelator: Self-assembly and rheology in various physiological conditions

Peptide-based supramolecular hydrogels as functional soft materials hold great promising for biomedical applications. However, much effort has been devoted to the finding and development of linear peptide hydrogelators and related hydrogel materials. Usually, linear peptide hydrogels are subject to the environmental variations and suffer from rapid enzymatic degradation in physiological conditions, limiting their more broad range of applications. Herein, we discover that a cyclic dipeptide (Cyclo-(Leu-Phe), CLF) can serve as a versatile hydrogelator for formation of supramolecular hydrogels at various physiological and harsh environments including the presence of salts, proteins and enzymes as well as acidic and basic aqueous solutions. Importantly, the CLF hydrogels show robust stability and excellent rheological properties at the various conditions, which are attributable to the rigid molecular structure of cyclic dipeptides and their strong 3-dimentional intermolecular hydrogen bonding networks. Hence, cyclic dipeptides provide a new alternative for development of peptide-based hydrogel materials with properties and functions more adapted for the complex and harsh environments.