Peptide contour length determines equilibrium secondary structure in protein-analogous micelles

Abstract

This work advances bottom-up design of bioinspired materials built from peptide-amphiphiles, which are a class of bioconjugates in which a biofunctional peptide is covalently attached to a hydrophobic moiety that drives self-assembly in aqueous solution. Specifically, this work highlights the importance of peptide contour length in determining the equilibrium secondary structure of the peptide as well as the self-assembled (i.e., micelle) geometry. Peptides used here repeat a seven-amino acid sequence between one and four times to vary peptide contour length while maintaining similar peptide-peptide interactions. Without a hydrophobic tail, these peptides all exhibit a combination of random coil and α-helical structure. Upon self-assembly in the crowded environment of a micellar corona, however, short peptides are prone to β-sheet structure and cylindrical micelle geometry while longer peptides remain helical in spheroidal micelles. The transition to β-sheets in short peptides is rapid, whereby amphiphiles first self-assemble with α-helical peptide structure, then transition to their equilibrium β-sheet structure at a rate that depends on both temperature and ionic strength. These results identify peptide contour length as an important control over equilibrium peptide secondary structure and micelle geometry. Furthermore, the time-dependent nature of the helix-to-sheet transition opens the door for shape-changing bioinspired materials with tunable conversion rates.