Hamiltonian Dynamics of Saturated Elongation in Amyloid Fiber Formation

Abstract

Elongation is a fundament process in amyloid fiber growth, which is normally characterized by a linear relationship between the fiber elongation rate and the monomer concentration. However, in high concentration regions, a sub-linear dependence was often observed, which could be explained by a universal saturation mechanism. In this paper, we modeled the saturated elongation process through a Michaelis-Menten like mechanism, which is constituted by two sub-steps -- unspecific association and dissociation of a monomer with the fibril end, and subsequent conformational change of the associated monomer to fit itself to the fibrillar structure. Typical saturation concentrations were found to be 7-70 M for A40, -synuclein and etc. Furthermore, by using a novel Hamiltonian formulation, analytical solutions valid for both weak and strong saturated conditions were constructed and applied to the fibrillation kinetics of -synuclein and silk fibroin.

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Reproductions