Molecular thermodynamics for protein precipitation with a polyelectrolyte

A molecular-thermodynamic framework is developed for phase equilibria in an aqueous system containing a charged globular protein and an oppositely cha rged linear polyelectrolyte. The globular protein is represented by a spher ical macroion with its colons; the linear polyelectrolyte is represented by a charged hard-sphere chain (polyion) with corresponding counterions. The potential of mean force contains Coulombic interactions between macroions, polyions, and small ions; long-range dispersion attractions between protein macroions; and hydrophobic macroion-polyion and macroion-macroion associat ions. Analytic expressions for thermodynamic properties are obtained, and l iquid-liquid phase equilibria (precipitation) are calculated for model syst ems. Adding polyelectrolyte to a protein solution leads to precipitation, b ut further addition of polyelectrolyte leads to redissolution of the protei n. This destabilization-restabilization phenomenon follows from electrostat ic interactions with coupled polymer adsorption. The effects on phase equil ibria of protein charge, protein size, association energy between protein-p olyion, polyion chain length, and polyion charge density are investigated f or model systems and compared with experimental data. Brief consideration i s given to fractional precipitation for binary aqueous mixtures of proteins with different charge densities.