True and apparent inhibition of amyloid fibril formation

Figures & data

Figure 1. The inhibition of amyloid fibrillization as predicted by the CLM for (A) sigmoidal and (B) hyperbolic aggregation kinetics. Black curves represent the normalized fibril mass increase as a function of time calculated using Equations 2(2) $$\frac{\Delta m}{\Delta m_T}=1-\frac{1}{k_{\text{b}}\left[\exp \right(k_{\text{a}}t)-1]+1}$$(2) and 3(3) $$\Delta m_T={\sigma }_{0}V{C}^{\ast }\gamma$$(3) , and using reference values of parameters k_a, k_b and γ: in (A) k_a = 1 (units of time)^–1, k_b = 1 × 10–3 and γ = 1, and in (B) k_a = 0.1 (units of time)^–1, k_b = 10 and γ = 1. Blue and red curves represent the inhibition of the nucleation and growth steps, respectively; green curves represent the apparent inhibition that results from changing the solution activity of the protein. The variation of parameters k_a, k_b and γ relatively to the reference values is indicated by the text next to the curves.

Figure 2. The thermodynamic effect provoked by the presence of PTFE balls during amyloidogenic incubation of αSyn. (A) The evolution of the thioflavin T fluorescence signal measured by Pronchik et al.²⁸ and digitized by us shows increasing reaction extents as the number of PTFE balls increases from 10 (▲) to 20 (□) to 50 (●). Reprinted with permission from Pronchik et al.²⁸ Copyright 2012 American Chemical Society. (B) By normalizing the results shown in (A) by the final fluorescence signal of each experiment the differences between kinetics become hardly visible; Equation 2(2) $$\frac{\Delta m}{\Delta m_T}=1-\frac{1}{k_{\text{b}}\left[\exp \right(k_{\text{a}}t)-1]+1}$$(2) was fitted to the normalized results obtained with 10 PTFE balls (solid line) to obtain k_a = 0.121 h^–1 and k_b = 0.253.

Pronchik J, He X, Giurleo JT, Talaga DS. In vitro formation of amyloid from α-synuclein is dominated by reactions at hydrophobic interfaces. J Am Chem Soc 2010; 132:9797 - 803; http://dx.doi.org/10.1021/ja102896h; PMID: 20578692

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