Discovery of diverse peptide nanotube architecture from the self-assembly of designed amyloid-beta cassettes

Protein or peptide-based tubular structures, including ion channels and membrane pores, exist widely in nature. To date, non-natural amino acids have been incorporated to control tube size and homogeneity. In efforts to exploit the energetics of the Alzheimer Disease associated amyloid-beta (Abeta) fibrils, I discovered conditions for the construction of highly mono-dispersed peptide nanotubes from the self-assembly of short Abeta peptide cassettes.; Small angle neutron (SANS) and X-ray scattering (SAXS) defined the outer and inner radius of the Abeta(16-22) nanotubes formed in pH2 40% acetonitrile/water solution to contain a 44 nm inner cavity with 4 nm thick walls. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) images further confirmed the homogenous arrays of solvent filled nanotubes arising from a flat rectangular sheet, 130 nm wide by 4 nm thick. The sheet coils into helical ribbons, coiling sufficiently to form the final nanotubes. Isotope-editing IR and solid-state NMR defined the peptide arrays inside nanotubes in an antiparallel beta-sheet orientation with one residue shifted out-of-registry.; Characterization of the peptide arrays allowed nanotube assembly to be exquisitely controlled, creating a variety of mono-dispersed morphologies with distinct chemical and physical stabilities. These highly positive charged tube surfaces were demonstrated to template metallic nanowire fabrication. Additionally, these nanotubes can be bundled into aligned macroporous filaments with sulfate bridging. These self-assembling elements now define a minimal building block suitable for the construction of a range of functional nanodevices. Such robust and persistent self-assembling systems not only offer a unique, robust, and easily accessible scaffold for nanotechnology, but also a better understanding of the amyloid fibril structure has been obtained.