Antibody association in solution: cluster distributions and mechanisms

Area of Science:

• Biophysics
• Physical Chemistry
• Protein Science

Background:

• Understanding antibody solution behavior is crucial for therapeutic development.
• Factors influencing antibody molecule clustering and association impact drug efficacy.

Purpose of the Study:

• To investigate the relationship between antibody concentration and solution properties like viscosity and clustering.
• To evaluate theoretical models for predicting antibody solution behavior.

Main Methods:

• Measured viscosity, second virial coefficients, Kirkwood-Buff integrals, and cluster distributions for 19 monoclonal antibody (mAb) solutions.
• Modeled solutions using statistical-physics Wertheim liquid-solution theory with Y-shaped antibody representations.
• Analyzed antibody-antibody interactions and their impact on solution properties.

Main Results:

• High solution viscosity correlates with a greater number of antibody molecules per cluster.
• Viscosity is accurately predicted by the 2-body Kirkwood-Buff quantity (G22), not the second virial coefficient (B22).
• Theoretical predictions based on Wertheim theory align well with experimental protein-protein sticking energy.

Conclusions:

• The study establishes a link between molecular-level interactions and macroscopic solution properties for associating proteins.
• This framework aids in predicting and controlling antibody solution behavior for therapeutic applications.
• Insights into nucleation and propagation rates inform the development of antibody-based therapeutics.