Effects of salts, buffers and sucrose on protein–protein attractive and repulsive interactions

Abstract

Repulsion between proteins is an advantageous attribute in aqueous protein formulations as it enhances solubility, and reduces precipitation, opalescence and viscosity. The interaction parameter ($k_D$) of lysozyme in solution was measured using dynamic light scattering (DLS). $k_D$ is a measure of attraction and repulsion between particles. All anions tested caused a drop in the $k_D$ of lysozyme consistent with charge screening. The buffer, citrate caused the greatest negative impact on the $k_D$ value of lysozyme, possibly due to a combination of charge screening, charge reversal and non-covalent crosslinking of the lysozyme molecules. Conversely, histidine buffer, had the least impact on the $k_D$ value of lysozyme. The ionic and non-ionic tonicity modifiers, sodium chloride and sucrose, both reduced repulsion between lysozyme molecules in both citrate and histidine buffers.