Antibody association in solution : cluster distributions and mechanisms

Brudar, Sandi (author), Breydo, Leonid (author), Chung, Elisha (author), Dill, Ken A. (author), Ehterami, Nasim (author), Phadnis, Ketan (author), Senapati, Samir (author), Shameemb, Mohammed (author), Tang, Xiaolin (author), Tayyab, Muhammmad (author), Hribar-Lee, Barbara (author)

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.

• Language: English
• Keywords: aggregation, viscosity, G22, modeling, thermodynamic perturbation theory
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 9 str.
• Numbering: Vol. 16, no. 1, art. 2339582
• PID: 20.500.12556/RUL-156196
• UDC: 577.322
• ISSN on article: 1942-0862
• DOI: 10.1080/19420862.2024.2339582
• COBISS.SI-ID: 194752259
• Publication date in RUL: 13.05.2024

Record is a part of a journal

• Title: MAbs
• Shortened title: MAbs
• Publisher: Taylor & Francis
• ISSN: 1942-0862
• COBISS.SI-ID: 32489433

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: agregacija, viskoznost, G22, modeliranje, termodinamska perturbacijska teorija

Projects

• Funder: NIH - National Institutes of Health
• Project number: RM1GM135136