Combining Scattering Experiments and Colloid Theory to Characterize Charge Effects in Concentrated Antibody Solutions

• DOI: 10.1021/acs.molpharmaceut.3c01023
• Publication Date: 2024-04-25T13:05:54Z
• Authors: Alessandro Gulotta; Marco Polimeni; Samuel Lenton; Charles G. Starr; Anna Stradner; Emanuela Zaccarelli; Peter Schurtenberger
• Keywords: Electrostatics; Electrophoretic light scattering; Particle (ecology)

Charges and their contribution to protein–protein interactions are essential for the key structural dynamic properties of monoclonal antibody (mAb) solutions. In fact, they influence apparent molecular weight, static structure factor, collective diffusion coefficient, or relative viscosity, concentration dependence. Further, charges play an important role in colloidal stability mAbs. There exist standard experimental tools characterize mAb net charges, such as measurement electrophoretic mobility, second virial interaction parameter. However, resulting values difficult directly relate actual overall charge theoretical predictions based on its known structure. Here, we report results a systematic investigation solution charged IgG1 function ionic strength using combination measurements, light scattering, small-angle X-ray tracer particle-based microrheology. We analyze interpret established colloid theory coarse-grained computer simulations. discuss potential limits models description effects mAbs, particular pointing out importance incorporating shape anisotropy when attempting predict at high concentrations.