Atomic Scale Structure of Self-Assembled Lipidated Peptide Nanomaterials

beta-Peptides have great potential as novel biomaterials and therapeutic agents, due to their unique ability to self-assemble into low dimensional nanostructures, and their resistance to enzymatic degradation in vivo. However, the self-assembly mechanisms of beta-peptides, which possess increased flexibility due to the extra backbone methylene groups present within the constituent beta-amino acids, are not well understood due to inherent difficulties of observing their bottom-up growth pathway experimentally. A computational approach is presented for the bottom-up modelling of the self-assembled lipidated beta 3-peptides, from monomers, to oligomers, to supramolecular low-dimensional nanostructures, in all-atom detail. The approach is applied to elucidate the self-assembly mechanisms of recently discovered, distinct structural morphologies of low dimensional nanomaterials, assembled from lipidated beta 3-peptide monomers. The resultant structures of the nanobelts and the twisted fibrils are stable throughout subsequent unrestrained all-atom molecular dynamics simulations, and these assemblies display good agreement with the structural features obtained from X-ray fiber diffraction and atomic force microscopy data. This is the first reported, fully-atomistic model of a lipidated beta 3-peptide-based nanomaterial, and the computational approach developed here, in combination with experimental fiber diffraction analysis and atomic force microscopy, will be useful in elucidating the atomic scale structure of self-assembled peptide-based and other supramolecular nanomaterials. A bottom-up theoretical approach is reported to produce the first atomically resolved experimentally consistent model of lipidated beta-peptide nanomaterials. The beta-peptide materials possess long-term mechanical and chemical stability in vivo, and may be easily decorated with combinations of different biological cues. This unique combination of properties is conducive to control over the resultant beta-peptide fiber morphology and biocompatibility, thus providing a substantial advantage over traditional alpha-peptide-based materials. image