Redox modulated hydrogelation of a self-assembling short peptide amphiphile

Hydrogels resulting from the self-assembly of small peptides are smart nanobiomaterials as their nanostructuring can be readily tuned by environmental stimuli such as pH, ionic strength and temperature, thereby favoring their practical applications. This work reports experimental observations of formation of peptide hydrogels in response to the redox environment. Ac-I₃K-NH₂ is a short peptide amphiphile that readily self-assembles into long nanofibers and its gel formation occurs at concentrations of about 10 mmol/L. Introduction of a Cys residue into the hydrophilic region leads to a new molecule, Ac-I₃CGK-NH₂, that enables the formation of disulfide bonds between self-assembled nanofibers, thus favoring cross-linking and promoting hydrogel formation. Under oxidative environment, Ac-I₃CGK-NH₂ formed hydrogels at much lower concentrations (even at 0.5 mmol/L). Furthermore, the strength of the hydrogels could be easily tuned by switching between oxidative and reductive conditions and time. However, AFM, TEM, and CD measurements revealed little morphological and structural changes at molecular and nano dimensions, showing no apparent influence arising from the disulfide bond formation.