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.