Fig. 3. Aβ42 fibrils exhibit intermittent growth.
(a and b) Survival functions of the growth and pause durations with data fits using single exponential functions, suggesting that the switching between the growing state, where fibril ends are competent to elongate, and the paused state, where elongation is blocked, can be described by a two-state process. The growth duration does not show a dependence on temperature, whereas the duration of the paused state exhibits an inverse dependence on temperature. (c) Decreasing the temperature increases the duration of the paused state, decreasing the growth probability, Pgrow, suggesting that the pauses in growth are due to a kinetically trapped state at the fibril end, which blocks the further attachment of monomers. (d) Schematic of the intermittent growth process and possible energy landscape reflecting entry into the paused state. Light green circle – correctly docked monomer, light green square – incorrectly docked monomer.