Depletion and pair interactions of proteins in polymer solutions.

We study the depletion, pair interaction, and phase behavioral characteristics of proteins in polymer solutions. We use a McMillan–Mayer-like approach [W. G. McMillan, Jr. and J. E. Mayer, J. Chem. Phys. 13, 276 (1945)] to suggest that the depletion characteristics should be studied at an effective polymer concentration which is a function of both the average polymer and the protein concentrations. In the protein limit, we show that the volume of the polymer depletion layers exceeds the size of the proteins, leading to effective polymer concentrations typically in the semidilute and concentrated regimes even when the average polymer concentrations are in the dilute regimes. We propose an approximate approach that accounts for the multibody depletion overlaps, and use an accurate numerical solution of polymer mean-field theory to address depletion characteristics in these regimes which are characterized by both the importance of polymer interactions as well as the curvature of the proteins relative to the correlation length of polymers. We show that the depletion characteristics of the protein-polymer mixture can be quite different when viewed in this framework, and this can have profound consequences for the phase behavior of the mixture. Our theoretical predictions for the phase diagram match semiquantitatively with published experimental results. [ABSTRACT FROM AUTHOR]