Hydrophobic residues provide much of the thermodynamic driving force for the folding, self-assembly, and consequent hydrogelation of amphiphilic β-hairpin peptides. We investigate how the identity of hydrophobic side chains displayed from the hydrophobic face of these amphiphilic peptides influences their behavior to expound on the design criteria important to gel formation. Six peptides were designed that globally incorporate valine, aminobutyric acid, norvaline, norleucine, phenylalanine, or isoleucine on the hydrophobic face of the hairpin to study how systematic changes in hydrophobic content, β-sheet propensity, and aromaticity affect gelation. Circular dichroism (CD) spectroscopy indicates that hydrophobic content, rather than β-sheet propensity, dictates the temperature- and pH-dependent folding and assembly behavior of these peptides. Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) show that the local morphology of the fibrils formed via self-assembly is little affected by amino acid type. However, residue type does influence the propensity of peptide fibrils to undergo higher order assembly events. Oscillatory rheology shows that the mechanical rigidity of the peptide gels is highly influenced by residue type, but there is no apparent correlation between rigidity and residue hydrophobicity nor β-sheet propensity. Lastly, the large planar aromatic side chain of phenylalanine supports hairpin folding and assembly, affording a gel characterized by a rate of formation and storage modulus similar to the parent valine-containing peptide.
All Science Journal Classification (ASJC) codes
- Organic Chemistry
- Polymers and Plastics
- Inorganic Chemistry
- Materials Chemistry