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

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 tl, the efficiency of growth is represented by the growth rate kg. Here, I have analysed the absolute kg and tl values from a total of 298 samples prepared from insulin, glucagon and different sequence variants of the Alzheimerʹs Aβ(1-40) peptide. Although these samples differ in the conditions of aggregation, systematic comparison reveals an overall similarity in the plot of kg versus tl. The plot fits readily with the simple equation kg = α/tl and by using a proportionality factor α of 4.5. In contrast to the individual values of kg and tl 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.