Amyloid fibrils electronics

Progress in deducing more structural details of these fibers has instead been achieved using NMR, electron microscopy and electron diffraction. These studies reveal that the fibers contain small microcrystals of ordered regions of the polypeptide chains interspersed in a matrix of less ordered or disordered regions of the chains (Eigure 14.9). The microcrystals comprise about 30% of the protein in the fibers, are arranged in p sheets, are 70 to 100 nanometers in size, and contain trace amounts of calcium ions. It is not yet established if the p sheets are planar or twisted as proposed for the amyloid fibril discussed in the previous section. 

Sunde M, Blake C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 1997 50 123-159. 

Jimenez, J. L., Tennent, G., Pepys, M., and Saibil, H. R. (2001). Structural diversity of ex vivo amyloid fibrils studied by cryo-electron microscopy. /. Mol. Biol. 311, 241-247. 

Fig. 2. Electron micrographs highlighting the polymorphism of amyloid fibrils. (A) A single human calcitonin protofibril with a diameter of 4 nm (adapted from Bauer et al., 1995). (B) Different morphologies present in a transthyretin fibril preparation. Black arrowheads show oligomers of different sizes, the black arrow points to a 9- to 10-nm-wide fibril, and the white arrowhead marks an 4-nm-wide fibril (adapted from Cardoso et al., 2002). (C-F) Human amylin fibril ribbons (adapted from Goldsbury et al., 1997). (C) A single 5-nm-wide protofibril. (D-F) Ribbons containing two (D), three (E), or five (F) 5-nm-wide protofibrils. (G) A twisted ribbon made of four 5-nm-wide protofibril subunits of Api-40 (adapted from Goldsbury et al., 2000b). Scale bar, 50 nm (A-G).

Antzutkin, O. N., Leapman, R. D., Balbach, J. J., and Tycko, R. (2002). Supramolecular structural constraints on Alzheimer s beta-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance. Biochemistry 41, 15436-15450. 

Nielsen, E. H., Nybo, M., and Svehag, S. E. (1999). Electron microscopy of prefibrillar structures and amyloid fibrils. Methods Enzymol. 309, 191 196. 

Shirahama, T., and Cohen, A. S. (1967). High-resolution electron microscopic analysis of the amyloid fibril./ Cell Biol. 33, 679-708. 

Bouchard, M., Zurdo, J., Nettleton, E. J., Dobson, C. M., and Robinson, C. V. (2000). Formation of insulin amyloid fibrils followed by FTIR simultaneously with CD and electron microscopy. Protein Sri. 9, 1960-1967. 

Fig. 15 Schematic drawing of the formation of amyloid fibrils, (a) Monomeric insulin having an a-helical conformation, (b) [i-sheet (arrows) rich oligomers are being formed, (c) Amyloid fibrils having a diameter around 10 nm are being formed, (d) Higher magnification of the intrinsic repetitive (S-pIcatcd sheet structure of the amyloid fibril. The pictures were taken by transmission electron microscopy (TEM)...

Figure 10.4 Electron microscope image of negatively stained amyloid fibrils formed by islet amyloid polypeptide showing long, unbranching fibrils of 100 A in diameter (reproduced with permission from [4]).

In this section, the potential application for amyloid fibrils and other selfassembling fibrous protein structures are outlined. These include potential uses in electronics and photonics presented in Section 4.1, uses as platforms for the immobilization of enzymes and biosensors presented in Section 4.2, and uses as biocompatible materials presented in Section 4.3. Each of these applications makes use of the ability of polypeptides to self-assemble and form nanostructured materials, a process that can occur under aqueous conditions. These applications also seek to exploit the favorable properties of fibrils such as strength and durability, the ability to arrange ligands on a nanoscale, and their potential biocompatibility arising from the natural materials used for assembly. 

Another approach toward fibrillar nanowires has been taken by Baldwin and colleagues (2006), who assembled a porphyrin binding protein onto the surface of an amyloid fibril. This binding protein could incorporate heme to form a functional b-type cytochrome. These fibrils could be developed to create wires for electron transfer, similar to structures observed in nature that consist of chains of heme molecules. 

Jimenez JL, Guijarro JI, Orlova E, Zurdo J, Dobson CM, Sunde M, Saibil HR. Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. EMBO J. 1999 18 815-821. 

The seven-residue peptide A -acetyl-Lys-Leu-Val-Phe-Phe-Ala-Glu-NH2 is shown by electron microscopy to form highly ordered fibrils upon incubation of aqueous solutions. X-ray powder diffraction and optical birefringence measurements have confirmed that these are amyloid fibrils. The peptide conformation and supramolecular organization in fibrils were investigated by solid state NMR. ... 

It is known that many proteins and peptides aggregate into extended p sheet like structures [3], Formation of amyloid fibrils is recognized important not only in understanding of human diseases but also is found acceptable for development of ordered nanostructures with modifiable properties and applicable in biotechnology, material science, molecular electronics and related fields. 

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