Nucleation of amyloid fibrils

Abstract

We consider nucleation of amyloid fibrils in the case when the process occurs by the mechanism of direct polymerization of practically fully extended protein segments, i.e. beta-strands, into beta-sheets. Applying the classical nucleation theory, we derive a general expression for the work to form a nanosized amyloid fibril (protofilament) constituted of successively layered beta-sheets. Analysis of this expression reveals that with increasing its size, the fibril transforms from one-dimensional into two-dimensional aggregate in order to preserve the equilibrium shape corresponding to minimal formation work. We determine the size of the fibril nucleus, the fibril nucleation work and the fibril nucleation rate as explicit functions of the concentration and temperature of the protein solution. The results obtained are applicable to homogeneous nucleation which occurs when the solution is sufficiently pure and/or strongly supersaturated.

References in corpus (4)

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• Self-Templated Nucleation in Peptide and Protein aggregation
• Phase Diagram of alpha-Helical and beta-Sheet Forming Peptides
• Insight into the correlation between lag time and aggregation rate in the kinetics of protein aggregation

Cited by in corpus (11)

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• Reaction rate theory for supramolecular kinetics: application to protein aggregation
• Insights into the variability of nucleated amyloid polymerization by a minimalistic model of stochastic protein assembly
• Amyloid Fibril Solubility
• Sequence dependent aggregation of peptides and fibril formation
• Thermodynamics of amyloid formation and the role of intersheet interactions
• Modeling generic aspects of ideal fibril formation
• Volume term of work of critical nucleus formation in terms of chemical potential difference relative to equilibrium one
• Vanishing linear term in chemical potential difference in volume term of work of critical nucleus formation for phase transition without volume change