Stop-and-go kinetics in amyloid fibrillation

Abstract

Many human diseases are associated with protein aggregation and fibrillation. Using glucagon as a model system for protein fibrillation we show that fibrils grow in an intermittent fashion, with periods of growth followed by long pauses. Remarkably, even if the intrinsic transition rates vary considerably in each experiment, the probability of being in the growing (stopping) state is very close to 1/4 (3/4), suggesting the presence of 4 independent conformations of the fibril tip. We discuss this possibility in terms of existing structural knowledge