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

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.