Exploiting Amyloid Fibril Lamination for Nanotube Self-Assembly

Abstract

Fundamental questions about the relative arrangement of the beta-sheet arrays within amyloid fibrils remain central to both its structure and the mechanism of self-assembly. Recent computational analyses suggested that sheet-to-sheet lamination was limited by the length of the strand. On the basis of this hypothesis, a short seven-residue segment of the Alzheimer's disease-related Abeta peptide, Abeta(16-22), was allowed to self-assemble under conditions that maintained the basic amphiphilic character of Abeta. Indeed, the number increased over 20-fold to 130 laminates, giving homogeneous bilayer structures that supercoil into long robust nanotubes. Small-angle neutron scattering and X-ray scattering defined the outer and inner radii of the nanotubes in solution to contain a 44-nm inner cavity with 4-nm-thick walls. Atomic force microscopy and transmission electron microscopy images further confirmed these homogeneous arrays of solvent-filled nanotubes arising from a flat rectangular bilayer, 130 nm wide x 4 nm thick, with each bilayer leaflet composed of laminated beta-sheets. The corresponding backbone H-bonds are along the long axis, and beta-sheet lamination defines the 130-nm bilayer width. This bilayer coils to give the final nanotube. Such robust and persistent self-assembling nanotubes with positively charged surfaces of very different inner and outer curvature now offer a unique, robust, and easily accessible scaffold for nanotechnology.

Intrinsic defect formation in peptide self-assembly

“…9,10 Studied by various experimental techniques including fiber-XRD, Nuclear Magnetic Resonance, TEM, and AFM, peptides are known to be able to self-assemble into ordered structures, such as nanofibrils, nanoribbons, and nanotubes, through forming the primary structure of cross b tapes [11][12][13] and layer stacking of tapes onto the primary structure along the peptide side-chain direction. 14,15 In the light of their analogue in traditional materials, it is natural to infer that defects also play an essential role in biomaterials. Surprisingly, in contrast to the extensive studies on self-assembled morphologies of peptides, no studies so far have been devoted to their defects except a few marginal experimental observations.…”

Failure of Aβ(1-40) amyloid fibrils under tensile loading

“…According to earlier experimental and theoretical studies these mechanical properties are related to their molecular structure [10,12]. The exceptional mechanical properties of amyloids make them good candidates for a wide range of potential technological applications, and specifically as new bionanomaterials utilizing them as nanowires [13][14][15][16], gels [17][18][19][20][21], scaffolds and biotemplates [13,[22][23][24][25][26][27], liquid crystals [28], adhesives [29] and biofilm materials [30]. These applications often imply the functionalization of the amyloid fibrils with the introduction of additional elements, including enzymes, metal ions, fluorophores, biotin or cytochromes.…”

Modulating Amyloid Self-Assembly and Fibril Morphology with Zn(II)

“…Therefore, Zn 2+ reduces the nucleation time of self-assembly across the entire concentration range and transforms Aβ(13-21)K16A assembly into either fibrillar or ribbon/ tubular morphology. 17 Struck by the different morphologies accessible to Aβ(13-21)-K16A, we investigated the coordination environment of Zn 2+ in the different assemblies by X-ray absorption spectroscopy (XAS). The soluble assembled metal-Aβ complexes were separated by centrifugation, and the fibers/ribbons were investigated either as resuspended solutions or directly as hydrated pellets, both of which showed identical XAS spectra ( Figure S2).…”