Kinetic profiles of the aggregation of 10 μM of tau in the absence (black) and presence of increasing concentrations of (A) HSPB1 chaperone (1, 2, 5, and 10 μM; dark to light green), (B) DNAJA2 (0.5, 1, 2.5, 5, 7.5, and 10 μM; dark to light purple), or (C) DNAJB1 (0.5, 1, 2.5, 5, 7.5, and 10 μM; dark to light blue). Open circles represent experimental data, and solid lines represent the fit of the kinetic profiles where only the primary nucleation (kn, left) or elongation (kp, right) pathways are inhibited. Residuals of the fits are shown under each panel. The changes in the aggregation kinetics caused by HSPB1 fit well with the elongation rate being primarily affected by the chaperone (A, right) whereas the changes in tau aggregation kinetics caused by DNAJB1 can be best described by the reduction of primary nucleation rates (C, left). In the case of DNAJA2, the changes in aggregation kinetics cannot be well described by the delay of only primary nucleation (B, left) or only elongation (B, middle) rates. There is good agreement, however, between the experimental data and fits to the integrated rate law of combined seeded and unseeded, in which primary nucleation, elongation, and fragmentation events have been considered simultaneously (B, right). Data points represent the means of 3–5 independent measurements. (D) The changes in microscopic nucleation (top) and elongation (bottom) rate constants as a function of the concentration of the molecular chaperones, relative to tau alone.