Liquid‐liquid phase separations in aqueous solutions of globular proteins

Abstract

A simple statistical‐mechanical theory, known as the random‐phase approximation, is applied to study liquid‐liquid phase separations in solutions of globular proteins. Phase separation may be induced by addition of nonionic polymer or/and ordinary electrolytes. In this analysis, the osmotic‐attraction mechanism, whereby the depletion of “solvent” particles between two proteins causes an attractive force, is primarily responsible for phase separation. For one‐component models of protein solutions, the theory yields simple algebraic expressions for the equation of state and for the chemical potential of the protein. This analytical theory describes the observed solubility behavior of proteins, including the effect of protein and polymer size, protein charge and concentration, and concentration of simple electrolytes.

Optimized Baxter model of protein solutions: Electrostatics versus adhesion

“…This conclusion, by itself, is not new for it has been reached earlier by formulating numerical work incorporating short-range forces and screened electrostatics and comparing it with x-ray scattering 39,40 and liquid-liquid phase separation. [41][42][43] The merit of the current analysis is its transparency because it is analytical and it is based on a nonperturbative variational principle for general short-range potentials, so it may be readily generalized.…”

Osmotic pressures and second virial coefficients for aqueous saline solutions of lysozyme

“…Enhanced association between water and salt ions causes water to be stripped from the protein, thereby increasing hydrophobic attraction between protein molecules (Becker, 1995;Coen, 1995;Vlachy, 1992Vlachy, , 1993. Salts with these properties are called kosmotropes; they are effective at salting-out proteins.…”

Hydrogen-ion titrations of amino acids and proteins in solutions containing concentrated electrolyte

“…(1) 7 (2) and (3) The individual ni's are known from the amino-acid sequence of a given protein. These equilibria occur on the side chains of acidic or basic residues and at the amino and carboxyl termini of the amino-acid chain in the protein.…”

“…Salting-out, the precipitation of protein by high electrolyte concentration, is a commonly used technique. Experimental work and theoretical modeling are conducted to gain a quantitative understanding of the nature of protein interactions in concentrated salt solutions [1][2][3]. To support modeling efforts, it is important to quantify the dependence of protein net charge on solution pH at high salt ionic strength, e.g.…”