Multiscale Modeling of Protein Adsorption in Polymer-Grafted Ion Exchangers
|Institution:||University of Virginia|
|Keywords:||protein chromatography; multiscale modeling; molecular dynamics; simulation|
|Full text PDF:||http://libra.virginia.edu/catalog/libra-oa:8999|
This work examines how molecular properties affect protein adsorption in polymer-grafted ion exchange chromatography (IEC) resins, as predicted by multiscale computational modeling. Polymer-grafted IEC resins, which have charged polymers grafted into their pores, are widely used because they can enhance the protein binding capacity and adsorption kinetics relative to traditional macroporous resins with open pore structures. Multiscale modeling is used to elucidate the molecular details of protein adsorption and diffusion in a polymer-grafted pore and to predict how these molecular behaviors affect experimentally-relevant macroscopic adsorption properties. Our multiscale modeling approach combines molecular dynamics (MD) simulation of protein in an IEC pore with numerical simulation of mass transfer into a resin particle. The molecular models are designed based on both the known physical properties of the systems of interest and on the experimentally-observed adsorption behaviors for these systems. Initial simulations of lysozyme in both macroporous and polymer-grafted resin pores agree qualitatively with experiments, showing that the polymer grafts have a modest effect on the adsorption capacity relative to the macroporous resin, but can enhance the effective transport rate significantly when electrostatic interactions are strong. This behavior arises from the combination of enhanced protein partitioning into the polymer-filled pore space, and relatively fast diffusion of protein associated with the polymers. Additional studies predict that lysozyme’s adsorption capacity and kinetics can be enhanced by increasing either the resin’s polymer graft density or the per-polymer charge content, as both types of modifications increase the number of polymer ligands available for adsorption within the pore. Systems with higher polymer ligand contents also exhibit more diffuse adsorption fronts. In systems with a high charge content per polymer and a low protein loading, the polymers preferentially partition towards the surface due to favorable interactions with the surface-bound protein. Simulations of lysozyme with different net charges, BSA, and IgG1 predict that adsorption behaviors vary significantly with the properties of the protein. For the polymer-grafted system, protein partitioning into the pore space and the overall transport rate are predicted to increase with the charge of the protein. Analysis of the number of contacts made between protein molecules and polymer ligands and protein mobility in the polymer-filled pore support existing hypotheses on the chain delivery mechanism for diffusion in these systems.