Salt-Triggered Peptide Folding and Consequent Self-Assembly into Hydrogels with Tunable Modulus

Intramolecular folding events, triggered by the presence of salt, induce the self-assembly of β-hairpin peptides into hydrogel networks at physiological conditions. At pH 7.4 and low ionic strength solution conditions, dilute, homogeneous solutions of peptide (≤2 wt %) exhibit the viscosity of pure water. Circular dichroism spectroscopy shows that, at pH 7.4 in the absence of salt, peptides are unfolded. By raising the ionic strength of the solution, electrostatic interactions between charged amino acids within the peptide are screened, and a β-hairpin conformation is adopted. Folded β-hairpin molecules supramolecularly assemble via hydrophobic collapse and hydrogen bonding into a three-dimensional hydrogel network. FTIR and X-ray scattering data demonstrate that these hydrogels are rich in β-sheet. Dynamic oscillatory rheological measurements demonstrate that the resultant supramolecular structure forms an elastic material whose structure, and thus modulus, can be tuned by salt concentration and temperature. Storage moduli of hydrogels increase with increasing salt concentration. Robust hydrogelation is also observed in cell growth media at physiological conditions. Transmission electron microscopy reveals that the hydrogel elasticity arises from a network nanostructure consisting of semiflexible fibrillar assemblies.