Fig. 3: Concentration dependence of the molecular pathways of Aβ42 oligomer dynamics. | Nature Chemistry

Fig. 3: Concentration dependence of the molecular pathways of Aβ42 oligomer dynamics.

From: Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide

Fig. 3

ac, Experimental measurements of the time evolution of oligomeric populations at varying concentrations of Aβ42 reveal the concentration dependence of oligomer conversion. a, Global fit of the experimental oligomer concentration data for 2.5, 5 and 10 μM Aβ42 to the integrated rate law that corresponds to the model shown in Fig. 2c. Shaded areas indicate 68% confidence bands (see Supplementary Section 6 and Supplementary Tables 1 and 2 for a list of the fitting parameters). b, Concentration dependence of the fractional contribution of unconverted oligomers towards the reactive flux to mature fibrils. Error bars indicate standard deviation. c, Extracted reaction orders for oligomer formation, oligomer conversion and the overall two-step secondary nucleation. dh, Computer simulation model of the Aβ42-aggregation-probe concentration dependence of oligomer conversion. d, Possible protein (left) and aggregate (right) states in the computer model. e, Mechanism of secondary nucleation in the computer simulations: monomers adsorb onto the fibril surface and detach as oligomers, which then convert into fibrils in solution at a later time. However, based on the analysis of our experimental data, we cannot exclude the possibility that structural conversion and dissociation of Aβ42 oligomers occur in contact with, or close to, the fibril surface. f, Rate of conversion of detached oligomers at varying monomer concentrations. g, The fraction of converted oligomers in the total oligomer population at three different monomer concentrations. h, Reaction orders for oligomer formation, oligomer conversion and the overall two-step secondary nucleation as measured in the simulations.

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