Figure 4: Nucleation–conversion–polymerization description of tau aggregation.
From: A mechanistic model of tau amyloid aggregation based on direct observation of oligomers
(a) Coarse-grained on-pathway conversion model obtained from theoretical considerations (Supplementary Material). Initial formation of non-growth-competent oligomeric species x(t), of average length xa(t), occurs via a reaction of order nc in monomer concentration m(t). Formation of fibrils f(t), of average length fa(t), then proceeds via addition of monomer units in a reaction of first order in m(t). Rate constants (k) for these processes and their corresponding reverse reactions are labelled. (b) Oligomeric and (deduced) fibrillar concentrations during the aggregation of K18, K18-PP, K18-ΔK280 and K18-P301L tau. Data represent the average of —three to five independent experiments, and error bars indicate the s.d. of these. Best fits for coarse-grained nucleation–conversion–polymerization description for K18, K18-ΔK280 and K18-P301L are shown as solid lines. The dotted black curves indicate upper bounds for x(t) predicted from the simpler inadequate nucleation–polymerization model (see Methods).
