Self-assembly of protein amyloid: a competition between amorphous and ordered aggregation

TL;DR

This paper models the thermodynamic equilibrium of protein aggregation, considering both ordered amyloid fibrils and disordered micelles, to better understand factors influencing amyloid formation and fibrilization kinetics.

Contribution

It introduces a model that includes disordered aggregates alongside fibrils, providing new insights into the thermodynamics and kinetics of protein aggregation.

Findings

Disordered micelles and fibrils coexist at equilibrium.

Inclusion of disordered species clarifies amyloid-promoting factors.

The model explains variations in fibrilization kinetics.

Abstract

Protein aggregation in the form of amyloid fibrils has important biological and technological implications. Although the self-assembly process is highly efficient, aggregates not in the fibrillar form would also occur and it is important to include these disordered species when discussing the thermodynamic equilibrium behavior of the system. Here, we initiate such a task by considering a mixture of monomeric proteins and the corresponding aggregates in the disordered form (micelles) and in the fibrillar form (amyloid fibrils). Starting with a model on the respective binding free energies for these species, we calculate their concentrations at thermal equilibrium. We then discuss how the incorporation of the disordered structure furthers our understanding on the various amyloid promoting factors observed empirically, and on the kinetics of fibrilization.