A possible role of salt-induced intermediates in the liquid-liquid phase transitions of globular protein dispersions

TL;DR

This paper proposes a model explaining liquid-liquid phase transitions in water-salt globular protein dispersions, emphasizing the role of salt-induced intermediates and their impact on phase behavior and osmotic pressure.

Contribution

It introduces a temperature-dependent model of protein chemical potential differences and highlights the involvement of protein intermediates in phase transitions.

Findings

Protein intermediates influence phase microstructure formation.

Temperature dependence of chemical potentials correlates with critical points.

Nonideal osmotic pressure behavior explained by phase diagram analysis.

Abstract

A probable model of the liquid-liquid (L-L) type phase transitions in water-salt dispersions of native (N*, N) globular proteins in the temperature range between thermal (D*) and cold (D) denaturation has been proposed. Protein intermediates (I, I*) arising as a result of the ion non-equilibrium (de)sorption in the process of D <-> N and D* <-> N* transitions are assumed to be involved in the L-L micro-phase transition forming clusters and fibrils in the main phase of N and N* proteins. Thus, they compensate for their excess chemical potential (ChPot) caused by unbalanced distribution of adsorbed salt ions in protein structure as compared to N-protein. A temperature model is proposed for the behavior of ChPots (delta mui) of various states of the protein: low-temperature i = D, N, I and high-temperature i = D*, N*, I*, as well as the transition between them. On this basis, the temperature dependence of the solvent ChPot delta mu1 is proposed. The relationship between the extreme values of delta mu1 and the temperatures of the critical points (upper and lower critical solution temperatures) of L-L transitions is established. The reasons for the nonideal behavior of osmotic pressure at different temperatures in water-salt protein dispersions are discussed on the basis of the phase diagrams.