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

Area of Science:

• Biophysical Chemistry
• Colloid Science
• Protein Science

Background:

• Protein charges are critical for monoclonal antibody (mAb) solution properties, influencing structural and dynamic characteristics like molecular weight and viscosity.
• Existing methods for measuring mAb net charges lack direct correlation with theoretical predictions based on molecular structure.
• Colloidal stability of mAbs is significantly affected by charge interactions.

Purpose of the Study:

• To systematically investigate the solution properties of a charged IgG1 mAb.
• To analyze the influence of concentration and ionic strength on mAb behavior.
• To evaluate the effectiveness of colloid theory and computer simulations in describing charged mAb interactions.

Main Methods:

• Electrophoretic measurements
• Static and dynamic light scattering
• Small-angle X-ray scattering
• Tracer particle-based microrheology
• Coarse-grained computer simulations

Main Results:

• Experimental data were analyzed using established colloid theory and simulations.
• The study explored the concentration and ionic strength dependence of mAb solution properties.
• The limitations of current colloidal models in predicting charged mAb behavior were discussed.

Conclusions:

• Charge anisotropy and molecular shape are important factors for accurate modeling of charged mAb solution properties.
• Advanced models are needed to fully capture the complex interactions in concentrated mAb solutions.
• This research provides insights into predicting and controlling mAb behavior in solution.