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Analysis of Protein Complex Formation at Micromolar Concentrations by Coupling Microfluidics with Mass Photometry
Published on: January 26, 2024
Weak interactions govern the viscosity of concentrated antibody solutions: high-throughput analysis using the
Brian D Connolly1, Chris Petry, Sandeep Yadav
1Pharmaceutical Development, Genentech, Inc., South San Francisco, California, USA.
Biophysical Journal
|July 26, 2012
Summary
Predicting monoclonal antibody (mAb) solution viscosity is challenging. A new method shows the diffusion interaction parameter (k(D)) from dilute solutions accurately predicts concentrated mAb viscosity, aiding candidate selection.
Area of Science:
- Biochemistry
- Physical Chemistry
- Chemical Engineering
Background:
- Concentrated antibody solutions exhibit viscoelastic properties modulated by protein-protein interactions.
- Predicting concentrated antibody solution behavior from dilute solution properties is a significant challenge.
Purpose of the Study:
- To establish a correlation between dilute solution properties and the viscosity of concentrated monoclonal antibody (mAb) solutions.
- To evaluate the role of weak intermolecular interactions versus electroviscous effects on mAb solution viscosity.
Main Methods:
- Measured the diffusion interaction parameter (k(D)) for 29 different mAbs (IgG(1) and IgG(4)) across varying solvent conditions (low and high ion normality).
- Correlated k(D) values with the exponential coefficient describing viscosity-concentration profiles.
- Experimentally determined effective charge to assess the electroviscous effect.
Main Results:
- A strong linear correlation (|R| ≥ 0.9) was found between k(D) and the viscosity concentration profiles of mAb solutions.
- mAb solution viscosity showed a poor correlation (|R| ≤ 0.6) with the mAb net charge, particularly under low ion normality.
- Weak intermolecular interactions, not the electroviscous effect, were identified as the primary driver of viscoelastic behavior.
Conclusions:
- The diffusion interaction parameter (k(D)) is a reliable predictor of concentrated mAb solution viscosity.
- This finding challenges the prevailing notion of the electroviscous effect's dominance in governing mAb viscoelasticity.
- The k(D) measurement serves as a valuable high-throughput screening tool for selecting mAbs with optimal viscosity properties early in development.
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