Morphological development of beta(1-40) amyloid fibrils.
The Alzheimer's disease-related peptide beta(1-40) amyloid self-associates to form fibrils exhibiting a morphology characteristic of amyloidogenic proteins. The mechanism of this fibrillization process has yet to be fully elucidated. In this study we have immobilized the beta(1-40) amyloid to flat gold surfaces using thiol-based self-assembled monolayers. Atomic force microscopy reveals the presence of spherical units of beta(1-40) amyloid immediately following the initiation of fibrillization. Short fibrillar structures, termed nascent fibrils, which appear to be formed by the association of these units are also present at this time point. At later time points extended, branching networks of fibrils are observed. Some fibrils exhibit a more beaded appearance and greater axial periodicity than others. No nascent fibrils are seen to be present. We believe that these data identify an early fibril structure which could act as an intermediate in beta-amyloid fibrillization. The oligomeric units of which these nascent fibrils are comprised are also determined.
Laboratory of Biophysics and Surface Analysis, School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom.
H K
HK
Blackley
N
N
Patel
M C
MC
Davies
C J
CJ
Roberts
S J
SJ
Tendler
M J
MJ
Wilkinson
P M
PM
Williams
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D009454:Neurofibrils / Q000648:ultrastructure*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)