Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence.

In order to elucidate design principles for biocompatible materials that can be created by in situ transformation from self-assembling oligopeptides, we investigate a class of oligopeptides that can self-assemble in salt solutions to form three-dimensional matrices. This class of peptides possesses a repeated sequence of amino acid residues with the type: hydrophobic/negatively-charged/hydrophobic/positively-charged. We systematically vary three chief aspects of this sequence type: (1) the hydrophobic side chains: (2) the charged side-chains: and (3) the number of repeats. Employing a rheometric assay to judge matrix formation, we determine the critical concentration of NaCl salt solution required to drive transformation from viscous state to gel state. We find that increasing side-chain hydrophobicity decreases the critical salt concentration in accord with our previous validation of DLVO theory for explaining this self-assembly phenomenon Caplan et al. (Biomacromolecules 1 (2000) 627). Further, we find that increasing the number of repeats yields a biphasic dependence-first decreasing, then increasing, the critical salt concentration. We believe that this result is likely due to an unequal competition between a greater hydrophobic (favorable) effect and a greater entropic (unfavorable) effect as the peptide length is increased. Finally, we find that we can use this understanding to rationally alter the charged side-chains to create a self-assembling oligopeptide sequence that at pH 7 remains viscous in the absence of salt but gels in the presence of physiological salt concentrations, a highly useful property for technological applications.