Engineering of peptide β-sheet nanotapes

Abstract

A set of principles are outlined for the design of short oligopeptides which will self-assemble in appropriate solvents into long, semi-flexible, polymericβ-sheet nanotapes. Their validity is demonstrated by experimental studies of an 11-residue peptide (DN1) which forms nanotapes in water, and a 24-residue peptide (K24) which forms nanotapes in non-aqueous solvents such as methanol. Circular dichroism (CD) spectroscopy studies of the self-assembly behaviour in very dilute solutions (µm) reveal a simple transition from a random coil-to-β-sheet conformation in the case of DN1, but a more complex situation for K24. Association of DN1 is very weak up to a concentration of 40 µm at which there is a sudden increase in the fraction of peptide in the β-sheet structure, indicative of an apparent ‘critical tape concentration’. This is shown to arise from a two-step self-assembly process: the first step being a transition from a random coil to an extended β-strand conformation, and the second the addition of this β-strand to a growing β-sheet. Both peptides are shown to gel their solvents at concentrations above 2×10 ^-3 volume fraction: these gels are stable up to the boiling point of the solvents. Rheology measurements on gels of the 24-residue peptide in 2-chloroethanol reveal that the tapes form an entangled network with a mesh size of 10–100 nm for peptide volume fractions 0.03–0.003; the persistence length of the tape is 13 nm or greater, indicative of a moderately rigid polymer; the tapes are about a single molecule in thickness. The mechanical properties of the gels in many respects are comparable to those of natural biopolymers such as gelatin, actin, amylose and agarose.