Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers.

Often nanostructures formed by self-assembly of small molecules based on hydrophobic interactions are rather unstable, causing morphological changes or even dissolution when exposed to changes in aqueous media. In contrast, peptides offer precise control of the nanostructure through a range of molecular interactions where physical stability can be engineered in and, to a certain extent, decoupled from size via rational design. Here, we investigate a family of peptides that form beta-sheet nanofibers and demonstrate a remarkable physical stability even after attachment of poly(ethylene glycol). We employed small-angle neutron/X-ray scattering, circular dichroism spectroscopy, and molecular dynamics simulation techniques to investigate the detailed nanostructure, stability, and molecular exchange. The results for the most stable sequence did not reveal any structural alterations or unimer exchange for temperatures up to 85 °C in the biologically relevant pH range. Only under severe mechanical perturbation (i.e., tip sonication) would the fibers break up, which is reflected in a very high activation barrier for unimer exchange of ∼320 kJ/mol extracted from simulations. The results give important insight into the relation between molecular structure and stability of peptide nanostructure that is important for, e.g., biomedical applications.