(687h) Elucidating the Details of Protein Transport in Polymer-Grafted Ion Exchangers Through Multi-Scale Modeling

In protein separations using ion-exchange chromatography, matrices with pores containing charged polymer grafts have exhibited increased binding capacity, faster adsorption kinetics, and a different diffusion mechanism as opposed to traditional macroporous matrices, though these enhancements depend strongly on the protein properties and concentration, as well as the buffer salt concentration. We use multi-scale modeling to study the factors which affect protein transport in polymer-grafted and macroporous materials, which in general depends on both the equilibrium adsorption and diffusion behavior of proteins in the different phases.

We have developed coarse-grained molecular models suitable for molecular dynamics (MD) simulations of proteins diffusing through representative pores of both polymer-grafted and macroporous materials. In simulations of lysozyme interacting with agarose-based matrices with charged dextran polymers, we obtain good agreement with experimental results for equilibrium binding capacities and effective transport rates, as well as their dependence on system parameters such as polymer graft density and surface topology.

The kinetic and equilibrium information from these MD simulations is also employed in a simple rate model to study the macroscopic protein concentration profiles in the different materials over time. With this model we observe faster adsorption kinetics and a different adsorption front for the polymer-grafted material as compared to the macroporous material, which is qualitatively consistent with experiments. We apply this multi-scale modeling approach to different types of proteins and adsorbed phases, as understanding how protein transport rates are affected by various protein and material properties should provide insight into the general mechanism by which charged polymers can enhance chromatographic performance.