Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However， complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far， which is a substantial obstacle to their rational design. In the absence of precise information， nanovesicles built of amphiphilic "lipid-like" peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. Using the nanocarrier formed by the amphiphilic self-assembling peptide 2 (SA2 peptide) as an example， we derive the local and global organization of a multimega-Dalton peptide-based nanocarrier at... More
Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However， complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far， which is a substantial obstacle to their rational design. In the absence of precise information， nanovesicles built of amphiphilic "lipid-like" peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. Using the nanocarrier formed by the amphiphilic self-assembling peptide 2 (SA2 peptide) as an example， we derive the local and global organization of a multimega-Dalton peptide-based nanocarrier at high molecular detail and at close-to physiological conditions. By integrating a multitude of experimental techniques (solid-state NMR， AFM， SLS， DLS， FT-IR， CD) with large- and multiscale MD simulations， we show that SA2 nanocarriers are built of interdigitated antiparallel β-sheets， which bear little resemblance to phospholipid liposomes. Our atomic level study allows analyzing the vesicle surface structure and dynamics as well as the intermolecular forces between peptides， providing a number of potential leads to improve and tune the biophysical properties of the nanocarrier. The herein presented approach may be of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions.
