Self-Interactions of Two Monoclonal Antibodies : Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling
(2022) In Molecular Pharmaceutics 19(2). p.508-519- Abstract
Using light scattering (LS), small-angle X-ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a two-protein model to predict B22. By comparing simulation and experimental results, we validated our models and obtained insights... (More)
Using light scattering (LS), small-angle X-ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a two-protein model to predict B22. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability.
(Less)
- author
- Mahapatra, Sujata ; Polimeni, Marco LU ; Gentiluomo, Lorenzo ; Roessner, Dierk ; Frieß, Wolfgang ; Peters, Günther H. J. ; Streicher, Werner W. ; Lund, Mikael LU and Harris, Pernille
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- colloidal stability, course-grained modeling, light scattering, monoclonal antibodies, Monte Carlo simulations, osmotic second virial coefficient, protein aggregation, small-angle X-ray scattering, structure factor
- in
- Molecular Pharmaceutics
- volume
- 19
- issue
- 2
- pages
- 508 - 519
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:85122316640
- pmid:34939811
- ISSN
- 1543-8384
- DOI
- 10.1021/acs.molpharmaceut.1c00627
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 American Chemical Society.
- id
- a1121d9a-028d-4792-a6bc-141ce781b697
- date added to LUP
- 2022-01-20 10:00:26
- date last changed
- 2024-04-06 16:44:11
@article{a1121d9a-028d-4792-a6bc-141ce781b697, abstract = {{<p>Using light scattering (LS), small-angle X-ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B<sub>22</sub>, and the molecular weight, M<sub>w</sub>, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a two-protein model to predict B<sub>22</sub>. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability. </p>}}, author = {{Mahapatra, Sujata and Polimeni, Marco and Gentiluomo, Lorenzo and Roessner, Dierk and Frieß, Wolfgang and Peters, Günther H. J. and Streicher, Werner W. and Lund, Mikael and Harris, Pernille}}, issn = {{1543-8384}}, keywords = {{colloidal stability; course-grained modeling; light scattering; monoclonal antibodies; Monte Carlo simulations; osmotic second virial coefficient; protein aggregation; small-angle X-ray scattering; structure factor}}, language = {{eng}}, number = {{2}}, pages = {{508--519}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Molecular Pharmaceutics}}, title = {{Self-Interactions of Two Monoclonal Antibodies : Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling}}, url = {{http://dx.doi.org/10.1021/acs.molpharmaceut.1c00627}}, doi = {{10.1021/acs.molpharmaceut.1c00627}}, volume = {{19}}, year = {{2022}}, }