Exploiting Amyloid Fibril Lamination for Nanotube Self-Assembly

• Published in: Journal of the American Chemical Society 2003-05, Vol.125 (21), p.6391-6393
• Main Authors: Lu, Kun, Jacob, Jaby, Thiyagarajan, Pappannan, Conticello, Vincent P, Lynn, David G
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Amyloid - chemistry; Amyloid beta-Peptides - chemistry; Analytical chemistry; ATOMIC FORCE MICROSCOPY; Chemistry; Circular Dichroism; Exact sciences and technology; HYPOTHESIS; intense pulsed neutron source; Microscopy, Atomic Force; Miscellaneous; Nanotechnology - methods; NANOTUBES; NERVOUS SYSTEM DISEASES; Neutrons; Peptide Fragments - chemistry; PEPTIDES; PHYSICS OF ELEMENTARY PARTICLES AND FIELDS; SCATTERING; Scattering, Radiation; TRANSMISSION ELECTRON MICROSCOPY; X-Rays
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0341642

Fundamental questions about the relative arrangement of the β-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 Aβ peptide, Aβ(16−22), was allowed to self-assemble under conditions that maintained the basic amphiphilic character of Aβ. 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 × 4 nm thick, with each bilayer leaflet composed of laminated β-sheets. The corresponding backbone H-bonds are along the long axis, and β-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.