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

In order to elucidate design principles for biocompatible materials that ca n be created by in situ transformation from self assembling oligopeptides, we investigate a class of oligopeptides that can self-assemble in salt solu tions to form three-dimensional matrices. This class of peptides. possesses a repeated sequence of amino acid residues with the type: hydrophobic/nega tively-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 rheomet ric assay to judge matrix formation, we determine the critical concentratio n 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 D LVO theory for explaining this self-assembly phenomenon Caplan et al. (Biom acromolecules 1 (2000) 627). Further, we find that increasing the number of repeats yields a biphasic dependence-first decreasing, then increasing, th e critical salt concentration. We believe that this result is likely due to an unequal competition between a greater hydrophobic (favorable) effect an d a greater entropic (unfavorable) effect as the peptide length is increase d. Finally, we find that we can use this understanding to rationally alter the charged side-chains to create a self-assembling oligopeptide sequence t hat at pH 7 remains viscous in the absence of salt but gels in the presence of physiological salt concentrations, a highly useful property for technol ogical applications. (C) 2001 Elsevier Science Ltd. All rights reserved.