  Protein amyloidosis is a cytopathological process characterized by the
formation of highly beta-sheet-rich fibrils. How this process occurs and how to
prevent/treat the associated diseases are not completely understood. Here, we
carry out a theoretical investigation of sequence-independent beta-sheet
formation, based on recent findings regarding the cooperativity of
hydrogen-bond network formation. Our results strongly suggest that in vivo
beta-sheet aggregation is induced by inter-sheet stacking dynamics. This leads
to a prediction for the minimal length of susceptible polymer needed to form
such an aggregate. Remarkably, the prediction corresponds quite well with the
critical lengths detected in poly-glutamine-related diseases. Our work
therefore provides a theoretical framework capable of understanding the
underlying mechanism and shedding light on therapy strategies of protein
amyloidosis.
