Chapter 6
Interactions of Globular Colloids and Flexible Polymers
Downloaded via TUFTS UNIV on July 12, 2018 at 04:48:22 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
Understanding Protein Partitioning in Two-Phase Aqueous Polymer Systems 1
Nicholas L. Abbott , Daniel Blankschtein, and T. Alan Hatton Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 We review our recent work aimed at elucidating the molecular-level mechanisms responsible for the partitioning of globular proteins in two-phase aqueous poly(ethylene oxide) (PEO)-dextran systems using the theoretical tools of polymer-scaling concepts, statistical-thermodynamics, and liquid-state theory, as well as the complementary experimental techniques of equilibrium protein partitioning and small-angle neutron scattering (SANS). On the basis of scaling predictions and SANS measurements, we propose that certain experimentally observed protein partitioning behaviors arise from a crossover in the underlying structure of the PEO-rich solution phase from individually dispersed P E O coils to an extensively entangled PEO mesh. Accordingly, we have introduced a variety of molecular-level pictures to describe the interactions of globular proteins and flexible polymers in solution. The various physical pictures differ in the ways they incorporate (i) the polymer solution regime, (ii) the relative size of the protein and the polymer coil/mesh, and (iii) the nature of the energetic interaction between the flexible polymer chains and the globular protein molecules. We have explored each proposed physical picture through a scaling-thermodynamic formulation and a combined equation-of-state/Monte-Carlo approach, and predicted the associated protein partitioning behaviors. A comparison of the theoretical predictions with experimental protein partitioning measurements (using two-phase aqueous PEO-dextran systems or a diffusion cell) suggests that although the physical exclusion of the proteins by the polymers contributes to the observed protein partitioning behavior, other interactions also play a significant role. Specifically, we have predicted the existence of a weak attractive interaction between the polymers and the proteins which increases with protein size, R , where 17Å
