Thermal aggregation of immunoglobulin G depending on the charge state of protein-polyelectrolyte complexes

Protein-polyelectrolyte complexes (PPCs) exhibit opposite effects, both suppressing and promoting protein aggregation, depending on the type of components. For the application of PPCs as protein stabilization technology, these opposite effects must be controlled. In this study, we investigated the thermal aggregation of immunoglobulin G (IgG)-polyamino acid complexes to elucidate the relationship between the charge state of PPCs, evaluated by the zeta potential, and their opposite effects on the aggregation process, which were measured using a spectrophotometer. After heating the PPCs, with their zeta potential departing from neutral, the soluble fractions of IgG increased by about 60 % or more. Insoluble aggregation was likely suppressed because PPCs with highly charged surfaces tend to have difficulty associating with each other. Interestingly, after heating the PPCs, with their zeta potential approaching neutral, the monomer fractions of IgG increased to nearly 100 %. A lower charge on the PPC surface could lead to association between PPCs, resulting in a dense protein solution that stabilized the monomeric state of the protein. This simplicity of merely adjusting the surface charge of PPCs opens up a wide range of applications for controlling protein aggregation during PPC formation, a challenge that had previously been considered difficult to address.