Absolute Correlation between Lag Time and Growth Rate in the Spontaneous Formation of Several Amyloid-like Aggregates and Fibrils

Abstract

The formation of polypeptide aggregates, including amyloid fibrils and prions, is a biochemical process of considerable interest in the context of its association with ageing and neurodegeneration. Aggregation occurs typically with a lag phase and a growth phase that reflect an underlying nucleation-polymerisation mechanism. While the propensity of nucleation can be estimated from the lag time t l, the efficiency of growth is represented by the growth rate k g. Here, I have analysed the absolute k g and t l values from a total of 298 samples prepared from insulin, glucagon and different sequence variants of the Alzheimer's Aβ(1-40) peptide. Although these samples differ in the conditions of aggregation, systematic comparison reveals an overall similarity in the plot of k g versus t l. The plot fits readily with the simple equation k g = α/ t l and by using a proportionality factor α of 4.5. In contrast to the individual values of k g and t l that depend substantially on sequential and environmental parameters, α seems much less affected by such factors. These data suggest mechanistic similarities in the nucleation behaviour of different amyloid-like fibrils and aggregates.