Cryo-EM of Helical Polymers.

While the application of cryogenic electron microscopy (cryo-EM) to helical polymers in biology has a long history, due to the huge number of helical macromolecular assemblies in viruses, bacteria, archaea, and eukaryotes, the use of cryo-EM to study synthetic soft matter noncovalent polymers has been much more limited. This has mainly been due to the lack of familiarity with cryo-EM in the materials science and chemistry communities, in contrast to the fact that cryo-EM was developed as a biological technique. Nevertheless, the relatively few structures of self-assembled peptide nanotubes and ribbons solved at near-atomic resolution by cryo-EM have demonstrated that cryo-EM should be the method of choice for a structural analysis of synthetic helical filaments.

Deterministic chaos in the self-assembly of β sheet nanotubes from an amphipathic oligopeptide.

The self-assembly of designed peptides into filaments and other higher-order structures has been the focus of intense interest because of the potential for creating new biomaterials and biomedical devices. These peptide assemblies have also been used as models for understanding biological processes, such as the pathological formation of amyloid. We investigate the assembly of an octapeptide sequence, Ac-FKFEFKFE-NH, motivated by prior studies that demonstrated that this amphipathic β strand peptide self-assembled into fibrils and biocompatible hydrogels.

Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials.

The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture.