In-situ atomic force microscopy study of β-amyloid fibrillization

• Published in: Journal of molecular biology Vol. 298; no. 5; pp. 833 - 840
• Main Authors: Blackley, H.K.L, Sanders, G.H.W, Davies, M.C, Roberts, C.J, Tendler, S.J.B, Wilkinson, M.J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 19.05.2000
• Subjects: Adsorption; Aluminum Silicates; Alzheimer’s disease; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - ultrastructure; atomic force microscopy; Biopolymers - chemistry; Biopolymers - metabolism; fibril formation; Kinetics; Microscopy, Atomic Force; Models, Biological; Monte Carlo Method; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - ultrastructure; Protein Binding; Protein Structure, Quaternary; protofibril; Solutions; Time Factors; β-amyloid; protofibril; AFM; fibril formation; Alzheimer’s disease; atomic force microscopy; β-amyloid
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.2000.3711

We report the use of atomic force microscopy to observe the initial stages of β-amyloid fibrillization in situ. The growth of individual β-amyloid protofibrils on a mica substrate was followed over several hours. The first in situ visualization of protofibril formation from single aggregate units of β-amyloid is reported. The growth of these protofibrils through the subsequent addition of these aggregate units is also observed. Growth of the protofibrils is bi-directional and the outgrowth of protofibrils from a common amyloid/heterogeneous core is also observed. Elongation also occurred by the addition of protofibrils from solution. This data provides an exciting insight into the early stages of β-amyloid fibrillization and can be used to enhance the understanding of the mechanism(s) by which β-amyloid fibrillizes and may consequently enable inhibition of one or more stages of fibrillization as a potential therapeutic strategy.