Patchy Charge Distribution Affects the pH in Protein Solutions During Dialysis

Explore how patchy charge distribution on protein surfaces influences pH variations during dialysis processes in this 19-minute conference lecture from the Workshop on "Charged Soft Matter: Bridging Theory and Experiment" at the Erwin Schrödinger International Institute. Discover why achieving target pH levels in protein purification through dialysis or ultra/diafiltration remains challenging, as the pH in the permeate differs from that in the protein-containing retentate. Learn about a novel computational model using colloidal particles with weakly acidic surface sites organized in patches, which systematically demonstrates how interactions between ionizable sites significantly affect nanoparticle charge and contribute to pH differences between permeate and retentate. Understand through molecular simulations in the Grand-Reaction ensemble how the significance of these interactions increases when ionizable sites are concentrated in smaller patches. Gain insights into why current dialysis models that account for Donnan equilibrium, acid-base properties, and ion-protein interactions fall short by neglecting the patchy distribution of ionizable groups, and discover how this research demonstrates that quantitative pH prediction models for protein solutions during dialysis must incorporate the patchy distribution of ionizable sites on protein surfaces to achieve accuracy in industrial purification processes.