ArticleJournal of molecular liquids2018
Controlling the viscosities of antibody solutions through control of their binding sites.
Article in Journal of molecular liquids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- BioMThermDB 1.0: Thermophysical Database of Proteins in Solutions.International journal of molecular sciences · 2022Pooled it
- Fab-Fc and Fab-Fab interactions of variable strength and valency contribute to the high concentration viscosity of IgGProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Electrostatics and viscosity are strongly linked in concentrated antibody solutions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Computational Procedure for Predicting Excipient Effects on Protein-Protein Affinities.Journal of chemical theory and computation · 2024Article
- Prediction of Antibody Viscosity from Dilute Solution Measurements.Antibodies (Basel, Switzerland) · 2023Article
- Protein Association in Solution: Statistical Mechanical Modeling.Biomolecules · 2023Review
- The Relationship between Protein-Protein Interactions and Liquid-Liquid Phase Separation for Monoclonal Antibodies.Molecular pharmaceutics · 2023Article
- Conformational Changes and Drivers of Monoclonal Antibody Liquid-Liquid Phase Separation.Journal of pharmaceutical sciences · 2023Article
- The influence of excipients on the viscosity of monoclonal antibody solutions.Journal of molecular liquids · 2022Article
- The Protein Folding Problem: The Role of Theory.Journal of molecular biology · 2021Review
- Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies.Polymers · 2021Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Multiscale Coarse-Grained Approach to Investigate Self-Association of Antibodies.Biophysical journal · 2020Article
- Cluster Formation and Entanglement in the Rheology of Antibody Solutions.The journal of physical chemistry. B · 2019Article
- Modeling the depletion effect caused by an addition of polymer to monoclonal antibody solutions.Journal of physics. Condensed matter : an Institute of Physics journal · 2018Article
- Theory for the Liquid-Liquid Phase Separation in Aqueous Antibody Solutions.The journal of physical chemistry. B · 2018Article
- Article
- Article
- Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
For biotechnological drugs, it is desirable to formulate antibody solutions with low viscosities. We go beyond previous colloid theories in treating protein-protein self-association of molecules that are antibody-shaped and flexible and have spatially specific binding sites. We consider interactions either through fragment antigen (Fab-Fab) or fragment crystalizable (Fab-Fc) binding. Wertheim's theory is adapted to compute the cluster-size distributions, viscosities, second virial coefficients, and Huggins coefficients, as functions of antibody concentration. We find that the aggregation properties of concentrated solutions can be anticipated from simpler-to-measure dilute solutions. A principal finding is that aggregation is controllable, in principle, through modifying the antibody itself, and not just the solution it is dissolved in. In particular: (i) monospecific antibodies having two identical Fab arms can form linear chains with intermediate viscosities. (ii) Bispecific antibodies having different Fab arms can, in some cases, only dimerize, having low viscosities. (iii) Arm-to-Fc binding allows for three binding partners, leading to networks and high viscosities.
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Registered trials
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