Competition between folding and aggregation in a model for protein solutions

TL;DR

This paper models the competition between protein folding and aggregation, revealing phase coexistence, stability conditions, and aggregation dynamics, which are crucial for understanding protein solution behaviors.

Contribution

It introduces a phenomenological model capturing thermodynamic and kinetic aspects of folding versus aggregation in proteins, highlighting phase diagrams and dynamic behaviors.

Findings

Phase coexistence between aggregated misfolded proteins and isolated proteins.

Non-monotonic temperature dependence of solution stability at low concentrations.

Aggregation dynamics influenced by folding states and quenching processes.

Abstract

We study the thermodynamic and kinetic consequences of the competition between single-protein folding and protein-protein aggregation using a phenomenological model, in which the proteins can be in the unfolded (U), misfolded (M) or folded (F) states. The phase diagram shows the coexistence between a phase with aggregates of misfolded proteins and a phase of isolated proteins (U or F) in solution. The spinodal at low protein concentrations shows non-monotonic behavior with temperature, with implications for the stability of solutions of folded proteins at low temperatures. We follow the dynamics upon "quenching" from the U-phase (cooling) or the F-phase (heating) to the metastable or unstable part of the phase diagram that results in aggregation. We describe how interesting consequences to the distribution of aggregate size, and growth kinetics arise from the competition between folding and aggregation.