Stepwise dynamics of epitaxially growing single amyloid fibrils.
The assembly mechanisms of amyloid fibrils, tissue deposits in a variety of degenerative diseases, is poorly understood. With a simply modified application of the atomic force microscope, we monitored the growth, on mica surface, of individual fibrils of the amyloid beta25-35 peptide with near-subunit spatial and subsecond temporal resolution. Fibril assembly was polarized and discontinuous. Bursts of rapid (up to 300-nm(-1)) growth phases that extended the fibril by approximately 7 nm or its integer multiples were interrupted with pauses. Stepwise dynamics were also observed for amyloid beta1-42 fibrils growing on graphite, suggesting that the discontinuous assembly mechanisms may be a general feature of epitaxial amyloid growth. Amyloid assembly may thus involve fluctuation between a fast-growing and a blocked state in which the fibril is kinetically trapped because of intrinsic structural features. The used scanning-force kymography method may be adapted to analyze the assembly dynamics of a wide range of linear biopolymers.
Kellermayer
Miklós S Z
MS
Department of Biophysics, Faculty of Medicine, University of Pécs, Szigeti út 12, H-7624, Pécs, Hungary. miklos.kellermayer.jr@aok.pte.hu
Karsai
Arpád
A
Benke
Margit
M
Soós
Katalin
K
Penke
Botond
B
D000465:Algorithms; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D001703:Biophysics / Q000379:methods; D001704:Biopolymers / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D018625:Microscopy, Atomic Force / Q000379:methods; D009991:Oscillometry; D010455:Peptides / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry; D012984:Software; D013997:Time Factors
D000682:Amyloid; D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010455:Peptides