Figure 4.

Aggregation kinetics analysis reveals a specific effect of metal ions on fibril-end elongation, leading to an enhanced oligomer generation rate. (a–c) Global fit analysis of aggregation kinetics, here shown for 3 μM Aβ42 in the presence of 0 to 10 μM Cu(II) (from violet to red colors), reveals the best fit for the elongation rate, k₊, as the sole free fitting parameter. (d, e) From the global fit results, the nucleation rate of new nucleation units can be calculated, exhibiting a shift of the maximum of the reaction and an increased area under the curve with increasing Cu(II) concentration, corresponding to an increased number of new nucleation units. (f) Aggregation model based on kinetic analysis, showing a specific inhibitory effect on fibril-end elongation by Cu(II) (violet) that results in an increased generation rate for new nucleation units (oligomers) in the presence of Cu(II) (violet) compared to the absence of Cu(II) (black). The figure was modified with permission from ref (1). Copyright 2022 the authors. American Chemical Society.