title: Phase separation in solutions with specific and nonspecific interactions.
abstract: Protein solutions, which tend to be thermodynamically stable under physiological conditions, can demix into protein-enriched and protein-depleted phases when stressed. Using a lattice-gas model of proteins with both isotropic and specific, directional interactions, we calculate the critical conditions for phase separation for model proteins with up to four patches via Monte Carlo simulations and statistical associating fluid theory. Given a fixed specific interaction strength, the critical value of the isotropic energy, which accounts for dispersion forces and nonspecific interactions, measures the stability of the solution with respect to nonspecific interactions. Phase separation is suppressed by the formation of protein complexes, which effectively passivate the strongly associating sites on the monomers. Nevertheless, we find that protein models with three or more patches can form extended aggregates that phase separate despite the assembly of passivated complexes, even in the absence of nonspecific interactions. We present a unified view of the critical behavior of model fluids with anisotropic interactions, and we discuss the implications of these results for the thermodynamic stability of protein solutions.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: William M
authors.initials: WM
authors.lastname: Jacobs
authors.affiliation: Pomona College, 550 North College Avenue, Claremont, California 91711, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Oxtoby
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Daan
authors.initials: D
authors.lastname: Frenkel
mesh_terms: D016880:Anisotropy; D003198:Computer Simulation; D003460:Crystallization; D008962:Models, Theoretical; D009010:Monte Carlo Method; D044367:Phase Transition; D012996:Solutions / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D012996:Solutions