Identifying the Coiled-Coil Triple Helix Structure of β-Peptide Nanofibers at Atomic Resolution

Peptide self-assembly represents a powerful bottom-up approach to the fabrication of nanomaterials. β3-Peptides are non-natural peptides composed entirely of β-amino acids, which have an extra methylene in the backbone, and we reported fibers derived from the self-assembly of β3-peptides that adopt 14-helical structures. β3-Peptide assemblies represent a class of stable nanomaterials that can be used to generate bio- and magneto-responsive materials with proteolytic stability. However, the three-dimensional structure of many of these materials remains unknown. To develop structure-based criteria for the design of β3-peptide-based biomaterials with tailored function, we investigated the structure of a tri-β3-peptide nanoassembly by molecular dynamics simulations and X-ray fiber diffraction analysis. Diffraction data was collected from aligned fibrils formed by Ac-β3[LIA] in water and used to inform and validate the model structure. Models with 3-fold radial symmetry resulted in stable fibers with a triple-helical coiled-coil motif and measurable helical pitch and periodicity. The fiber models revealed a hydrophobic core and twist along the fiber axis arising from a maximization of contacts between hydrophobic groups of adjacent tripeptides on the solvent-exposed fiber surface. These atomic structures of macroscale fibers derived from β3-peptide-based materials provide valuable insight into the effects of the geometric placement of the side chains and the influence of solvent on the core fiber structure which is perpetuated in the superstructure morphology.