Mechanochemical coupling in synthetic polypeptides by modulation of an inverse temperature transition.

Publisher Website
Google Scholar
Abstract
For the polypentapeptide of elastin (L-Val-L-Pro-Gly-L-Val-Gly)n, and appropriate analogs when suitably crosslinked, it has been previously demonstrated that development of elastomeric force at fixed length and length changes at fixed load occur as the result of an inverse temperature transition, with the temperature of the transition being inversely dependent on the hydrophobicity of the polypeptide. This suggests that at fixed temperature a chemical means of reversibly changing the hydrophobicity could be used for mechanochemical coupling. Evidence for this mechanism of mechanochemical coupling is given here with a 4%-Glupolypentapeptide, in which the valine in position 4 is replaced in 1 out of 5 pentamers by a glutamic acid residue. Before cross-linking, the temperature for aggregation of 4%-Glupolypentapeptide is remarkably sensitive to pH, shifting from 25% at pH 2 to 70.degree.C at pH 7.4 in phosphate-buffered saline (PBSD). At 37.degree. C, the cross-linked 4%-Glu-polypentapeptide matrix in PBS undergoes a pH-modulated contraction and relaxation with a change from pH 4.3 to 3.3 and back. The mean distance between carboxylates at pH 4.3 in the elastomeric matrix is greater than 40 .ANG., twice the mean distance between negatively charged species in PBS. Accordingly, charge-charge repulsion is expected to make little or no contribution to the coupling. Mechanochemical coupling is demonstrated at fixed load by monitoring pH dependence of length and at constant length by monitoring pH dependence of force. To our knowledge, this the first demonstration of mechanochemical coupling in a synthetic polypeptide and the first system to provide a test of the recent proposal that chemical modulation of an inverse temperature transition can be a mechanism for mechanochemical coupling. It is suggested that phosphorylation and dephosphorylation may modulate structure and forces in proteins by locally shifting the temperatures of inverse temperature transitions.