  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. Remarkably,
the probability of being in the growing (stopping) state is very close to 1/4
(3/4) in all experiments, even if the rates vary considerably. This finding
suggests the presence of 4 independent conformations of the fibril tip; we
discuss this possibility in terms of the existing structural knowledge.
