Modular Design of Self-Assembling Peptide-Based Nanotubes

TLDR

Rational design of peptide‑based nanotubes with defined internal channels promises new biomaterials and deeper insight into peptide self‑assembly. The study demonstrates that blunt‑ended α‑helical barrels can serve as modular building blocks for peptide‑based nanotubes. The authors employ a systematic, de novo helical‑bundle strategy, assembling hexameric α‑helical barrels into highly ordered nanotubes whose structure was resolved by cryo‑EM, X‑ray fiber diffraction, and model building. The resolved structure shows that module symmetry governs assembly ordering, and the resulting nanotubes can sequester hydrophobic dye within their lumens.

Abstract

An ability to design peptide-based nanotubes (PNTs) rationally with defined and mutable internal channels would advance understanding of peptide self-assembly, and present new biomaterials for nanotechnology and medicine. PNTs have been made from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we show that blunt-ended α-helical barrels, that is, preassembled bundles of α-helices with central channels, can be used as building blocks for PNTs. This approach is general and systematic, and uses a set of de novo helical bundles as standards. One of these bundles, a hexameric α-helical barrel, assembles into highly ordered PNTs, for which we have determined a structure by combining cryo-transmission electron microscopy, X-ray fiber diffraction, and model building. The structure reveals that the overall symmetry of the peptide module plays a critical role in ripening and ordering of the supramolecular assembly. PNTs based on pentameric, hexameric, and heptameric α-helical barrels sequester hydrophobic dye within their lumens.