Antibody association in solution: cluster distributions and mechanisms
Understanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different monoclonal antibody (mAb) solutions, we measured the viscosities, the second virial coefficients, the Kirkwood-Buff integrals, and t...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2339582 |
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| _version_ | 1832576557198082048 |
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| author | Sandi Brudar Leonid Breydo Elisha Chung Ken A. Dill Nasim Ehterami Ketan Phadnis Samir Senapati Mohammed Shameem Xiaolin Tang Muhammmad Tayyab Barbara Hribar-Lee |
| author_facet | Sandi Brudar Leonid Breydo Elisha Chung Ken A. Dill Nasim Ehterami Ketan Phadnis Samir Senapati Mohammed Shameem Xiaolin Tang Muhammmad Tayyab Barbara Hribar-Lee |
| author_sort | Sandi Brudar |
| collection | DOAJ |
| description | Understanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different monoclonal antibody (mAb) solutions, we measured the viscosities, the second virial coefficients, the Kirkwood-Buff integrals, and the cluster distributions of the antibody molecules as functions of protein concentration. Solutions were modeled using the statistical-physics Wertheim liquid-solution theory, representing antibodies as Y-shaped molecular structures of seven beads each. We found that high-viscosity solutions result from more antibody molecules per cluster. Multi-body properties such as viscosity are well predicted experimentally by the 2-body Kirkwood-Buff quantity, G22, but not by the second virial coefficient, B22, and well-predicted theoretically from the Wertheim protein–protein sticking energy. Weakly interacting antibodies are rate-limited by nucleation; strongly interacting ones by propagation. This approach gives a way to relate micro to macro properties of solutions of associating proteins. |
| format | Article |
| id | doaj-art-8d762b7c24c345f59e346532165988ed |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-8d762b7c24c345f59e346532165988ed2025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2339582Antibody association in solution: cluster distributions and mechanismsSandi Brudar0Leonid Breydo1Elisha Chung2Ken A. Dill3Nasim Ehterami4Ketan Phadnis5Samir Senapati6Mohammed Shameem7Xiaolin Tang8Muhammmad Tayyab9Barbara Hribar-Lee10Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SloveniaFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USALaufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFormulation Development Group, Regeneron Pharmaceuticals, Tarrytown, NY, USAFaculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SloveniaUnderstanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different monoclonal antibody (mAb) solutions, we measured the viscosities, the second virial coefficients, the Kirkwood-Buff integrals, and the cluster distributions of the antibody molecules as functions of protein concentration. Solutions were modeled using the statistical-physics Wertheim liquid-solution theory, representing antibodies as Y-shaped molecular structures of seven beads each. We found that high-viscosity solutions result from more antibody molecules per cluster. Multi-body properties such as viscosity are well predicted experimentally by the 2-body Kirkwood-Buff quantity, G22, but not by the second virial coefficient, B22, and well-predicted theoretically from the Wertheim protein–protein sticking energy. Weakly interacting antibodies are rate-limited by nucleation; strongly interacting ones by propagation. This approach gives a way to relate micro to macro properties of solutions of associating proteins.https://www.tandfonline.com/doi/10.1080/19420862.2024.2339582AggregationviscosityG22modelingthermodynamic perturbation theory |
| spellingShingle | Sandi Brudar Leonid Breydo Elisha Chung Ken A. Dill Nasim Ehterami Ketan Phadnis Samir Senapati Mohammed Shameem Xiaolin Tang Muhammmad Tayyab Barbara Hribar-Lee Antibody association in solution: cluster distributions and mechanisms mAbs Aggregation viscosity G22 modeling thermodynamic perturbation theory |
| title | Antibody association in solution: cluster distributions and mechanisms |
| title_full | Antibody association in solution: cluster distributions and mechanisms |
| title_fullStr | Antibody association in solution: cluster distributions and mechanisms |
| title_full_unstemmed | Antibody association in solution: cluster distributions and mechanisms |
| title_short | Antibody association in solution: cluster distributions and mechanisms |
| title_sort | antibody association in solution cluster distributions and mechanisms |
| topic | Aggregation viscosity G22 modeling thermodynamic perturbation theory |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2339582 |
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