title: In-situ atomic force microscopy study of beta-amyloid fibrillization.
abstract: We report the use of atomic force microscopy to observe the initial stages of beta-amyloid fibrillization in situ. The growth of individual beta-amyloid protofibrils on a mica substrate was followed over several hours. The first in situ visualization of protofibril formation from single aggregate units of beta-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 beta-amyloid fibrillization and can be used to enhance the understanding of the mechanism(s) by which beta-amyloid fibrillizes and may consequently enable inhibition of one or more stages of fibrillization as a potential therapeutic strategy.
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmaceutical Sciences University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: H K
authors.initials: HK
authors.lastname: Blackley
authors.forename: G H
authors.initials: GH
authors.lastname: Sanders
authors.forename: M C
authors.initials: MC
authors.lastname: Davies
authors.forename: C J
authors.initials: CJ
authors.lastname: Roberts
authors.forename: S J
authors.initials: SJ
authors.lastname: Tendler
authors.forename: M J
authors.initials: MJ
authors.lastname: Wilkinson
mesh_terms: D000327:Adsorption; D000538:Aluminum Silicates; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D009010:Monte Carlo Method; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012996:Solutions; D013997:Time Factors
chemical_list: D000538:Aluminum Silicates; D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; D012996:Solutions; C078592:amyloid beta-protein (1-40); C011934:mica