Hamiltonian Dynamics of Saturated Elongation in Amyloid Fiber Formation

TL;DR

This paper models amyloid fiber elongation saturation using a Hamiltonian approach, revealing universal saturation behavior and providing analytical solutions for fibrillation kinetics.

Contribution

It introduces a Hamiltonian formulation for saturated elongation, offering new analytical solutions applicable to various fibrillation conditions.

Findings

Identified saturation concentrations for different amyloid proteins.

Developed a Hamiltonian model capturing both weak and strong saturation regimes.

Applied the model to α-synuclein and silk fibroin fibrillation kinetics.

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 $7-70\mu M$ for A$\beta$40, $\alpha$-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 $\alpha$-synuclein and silk fibroin.