Modeling of protein interactions with surface-grafted charged polymers. Correlations between statistical molecular modeling and a mean field approach.
Ion exchange media involving charge groups attached to flexible polymers are widely used for protein purification. Such media often provide enhanced target protein purity and yield. Yet, little is understood about protein interaction with such media at the molecular level, or how different media architectures might affect separation performance. To gain a better understanding of such adsorptive systems, statistical mechanical perturbation calculations, utilizing a Debye-Hückel potential, were performed on surface-grafted charged polymers and their interaction with model proteins. The studied systems were weakly charged, and the polymers were linear and relatively short (degree of polymerization is 30). Segment distributions from the surface were also determined. The interaction of spherical model protein particles of 12-30 A radius were investigated with respect to polymer grafting density, distance from matrix surface, protein charge, and ionic strength. The partitioning coefficient of the model proteins was determined for different distances from the surface. An empirical mean field theory that scales the entropy of the protein with the square of the protein radius correlates well to Monte Carlo statistical modeling results. Upon adsorption to the polymer layers, the model proteins exhibit a critical surface charge density that is proportional to the ionic strength, independent of the grafting density, and appears to be a fundamental determinant of protein adsorption. Partitioning of protein-like nanoparticles to the charged polymer surface is only favored above the particle critical charge density.
Johansson
Hans-Olof
HO
Department of Biochemistry, University of Lund, P.O. Box 124, Lund, Sweden. hans-olof.johansson@biochemistry.lu.se
Van Alstine
James M
JM
D007477:Ions / Q000737:chemistry*; D008958:Models, Molecular; D009994:Osmolar Concentration; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties
D007477:Ions; D011108:Polymers; D011506:Proteins