| The ability of proteins to adopt discrete structures, as well as the ability of folded proteins to undergo supramolecular assembly, is based on the display of chemical functionality of the protein. Proteins fold and assemble according to the influence of intra- and intermolecular forces that act upon it to form ordered structures. By identifying these forces and how they influence assembly, they, in turn, can be exploited to design and synthesize materials from protein-based building blocks. By fabricating materials in this manner, the bulk material properties can be tuned by engineering at the molecular level. This study explores how modulation of the hydrophobic face of a de novo designed self-assembling beta-hairpin peptide affects its ability to fold and self-assemble to form a hydrogel, as well as on the resulting hydrogel's nanoscale structure and bulk properties. Initially, sequence modifications using amino acids of varying hydrophobicity were used to modify the hydrophobic face of the amphiphilic peptide. These modifications demonstrate how important hydrophobic regions of the peptide are to its ability to fold, self-assemble and form a hydrogel. The knowledge acquired from these studies was then used in the de novo design of a zinc-triggered peptide hydrogel, employing a nonnatural metal-binding amino acid on the hydrophobic face to instill metal-sensitivity in the peptide. Finally, aromatic interactions were incorporated on the topologically smooth hydrophobic face to direct self-assembly so as to impede the formation of interfibril junctions that lead to crosslinking of the fibrils that comprise the hydrogel scaffold. |
