Simulations of nucleation and elongation of amyloid fibrils.

摘要: We present a coarse-grained model for the growth kinetics of amyloid fibrils from solutions peptides and address fundamental mechanism nucleation elongation by using lattice Monte Carlo procedure. reproduce three main characteristics fibrils: (1) existence lag time, (2) occurrence critical concentration, (3) seeding. find to require quasi-two-dimensional configuration, where second layer β sheet must be formed adjunct first layer, which in turn leads highly cooperative barrier. The stage is found involve Ostwald ripening (evaporation-condensation) mechanism, whereby bigger grow at expense smaller ones. This new reconciles debate as whether protofibrils are precursors or monomer reservoirs. have systematically investigated roles peptide temperature, seed size. In general, we that there two kinds time arising different mechanisms. For higher temperatures low enough concentrations close disassembly boundary, fibrillization follows mechanism. However, temperatures, sufficiently short, still exists an apparent due slow Consequently, nonmonotonic with shortest occurring intermediate depend on concentration. While dominated regime can controlled seeding, insensitive Simulation results our fibril size, rate, solubility consistent available experimental observations many specific systems.