Application of a simple short-range attraction long-range repulsion colloidal model towards predicting the viscosity of protein solutions

Abstract: Some hard sphere colloidal models have been criticized for inaccurately predicting the solution viscosity of complex biological molecules like proteins. Competing short-range attractions and long-range repulsions, also known as SALR interactions, have been thought to affect the microstructure of a protein solution at low to moderate ionic strength. However, such interactions have been implicated primarily in causing phase transition, protein gelation, or reversible cluster formation and their effect on protein solution viscosity change is not fully understood. In this work we show the application of a hard sphere colloidal model with SALR interactions towards predicting the viscosity of dilute to semi-dilute protein solutions. The comparison is performed for a globular shaped albumin and Y-shaped therapeutic monoclonal antibody that are not explained by previous colloidal models. The model predictions show that it is the coupling between attractions and repulsions that give rise to the observed experimental trends in solution viscosity as a function of pH, concentration, and ionic strength. The parameters of the model are obtained from measurements of the second virial coefficient and net surface charge/zeta-potential, without additional fitting of the viscosity.