Stop-and-go kinetics in amyloid fibrillation.
Many human diseases are associated with protein aggregation and fibrillation. We present experiments on in vitro glucagon fibrillation using total internal reflection fluorescence microscopy, providing real-time measurements of single-fibril growth. We find that amyloid fibrils grow in an intermittent fashion, with periods of growth followed by long pauses. The observed exponential distributions of stop and growth times support a Markovian model, in which fibrils shift between the two states with specific rates. Even if the individual rates vary considerably, we observe that the probability of being in the growing (stopping) state is very close to 1/4 (3/4) in all experiments.
Ferkinghoff-Borg
Jesper
J
DTU Elektro, Building 349, Ørsteds Plads, Technical University of Denmark, 2800 Lyngby, Denmark. jfb@elektro.dtu.dk
Fonslet
Jesper
J
Andersen
Christian Beyschau
CB
Krishna
Sandeep
S
Pigolotti
Simone
S
Yagi
Hisashi
H
Goto
Yuji
Y
Otzen
Daniel
D
Jensen
Mogens H
MH
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D003460:Crystallization / Q000379:methods; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011487:Protein Conformation
D000682:Amyloid; D046912:Multiprotein Complexes