Combining Scattering Experiments and Colloid Theory to Characterize Charge Effects in Concentrated Antibody Solutions
Gulotta, Alessandro LU ; Polimeni, Marco LU ; Lenton, Samuel LU ; Starr, Charles G. ; Stradner, Anna LU ; Zaccarelli, Emanuela and Schurtenberger, Peter LU
(2023)
In Molecular Pharmaceutics
- Abstract
Charges and their contribution to protein-protein interactions are essential for the key structural and dynamic properties of monoclonal antibody (mAb) solutions. In fact, they influence the apparent molecular weight, the static structure factor, the collective diffusion coefficient, or the relative viscosity, and their concentration dependence. Further, charges play an important role in the colloidal stability of mAbs. There exist standard experimental tools to characterize mAb net charges, such as the measurement of the electrophoretic mobility, the second virial coefficient, or the diffusion interaction parameter. However, the resulting values are difficult to directly relate to the actual overall net charge of the antibody and to... (More)
Charges and their contribution to protein-protein interactions are essential for the key structural and dynamic properties of monoclonal antibody (mAb) solutions. In fact, they influence the apparent molecular weight, the static structure factor, the collective diffusion coefficient, or the relative viscosity, and their concentration dependence. Further, charges play an important role in the colloidal stability of mAbs. There exist standard experimental tools to characterize mAb net charges, such as the measurement of the electrophoretic mobility, the second virial coefficient, or the diffusion interaction parameter. However, the resulting values are difficult to directly relate to the actual overall net charge of the antibody and to theoretical predictions based on its known molecular structure. Here, we report the results of a systematic investigation of the solution properties of a charged IgG1 mAb as a function of concentration and ionic strength using a combination of electrophoretic measurements, static and dynamic light scattering, small-angle X-ray scattering, and tracer particle-based microrheology. We analyze and interpret the experimental results using established colloid theory and coarse-grained computer simulations. We discuss the potential and limits of colloidal models for the description of the interaction effects of charged mAbs, in particular pointing out the importance of incorporating shape and charge anisotropy when attempting to predict structural and dynamic solution properties at high concentrations.
(Less)
- author
- Gulotta, Alessandro
LU
; Polimeni, Marco
LU
; Lenton, Samuel
LU
; Starr, Charles G.
; Stradner, Anna
LU
; Zaccarelli, Emanuela
and Schurtenberger, Peter
LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- antibodies, charge effects, coarse-grained modeling, effective charge
- in
- Molecular Pharmaceutics
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:38661388
- scopus:85191976752
- ISSN
- 1543-8384
- DOI
- 10.1021/acs.molpharmaceut.3c01023
- language
- English
- LU publication?
- yes
- id
- c4edeba4-6877-4e9f-a50c-7e09fdc7bb74
- date added to LUP
- 2024-05-16 12:18:35
- date last changed
- 2024-05-30 14:10:45
@article{c4edeba4-6877-4e9f-a50c-7e09fdc7bb74,
abstract = {{<p>Charges and their contribution to protein-protein interactions are essential for the key structural and dynamic properties of monoclonal antibody (mAb) solutions. In fact, they influence the apparent molecular weight, the static structure factor, the collective diffusion coefficient, or the relative viscosity, and their concentration dependence. Further, charges play an important role in the colloidal stability of mAbs. There exist standard experimental tools to characterize mAb net charges, such as the measurement of the electrophoretic mobility, the second virial coefficient, or the diffusion interaction parameter. However, the resulting values are difficult to directly relate to the actual overall net charge of the antibody and to theoretical predictions based on its known molecular structure. Here, we report the results of a systematic investigation of the solution properties of a charged IgG1 mAb as a function of concentration and ionic strength using a combination of electrophoretic measurements, static and dynamic light scattering, small-angle X-ray scattering, and tracer particle-based microrheology. We analyze and interpret the experimental results using established colloid theory and coarse-grained computer simulations. We discuss the potential and limits of colloidal models for the description of the interaction effects of charged mAbs, in particular pointing out the importance of incorporating shape and charge anisotropy when attempting to predict structural and dynamic solution properties at high concentrations.</p>}},
author = {{Gulotta, Alessandro and Polimeni, Marco and Lenton, Samuel and Starr, Charles G. and Stradner, Anna and Zaccarelli, Emanuela and Schurtenberger, Peter}},
issn = {{1543-8384}},
keywords = {{antibodies; charge effects; coarse-grained modeling; effective charge}},
language = {{eng}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Molecular Pharmaceutics}},
title = {{Combining Scattering Experiments and Colloid Theory to Characterize Charge Effects in Concentrated Antibody Solutions}},
url = {{http://dx.doi.org/10.1021/acs.molpharmaceut.3c01023}},
doi = {{10.1021/acs.molpharmaceut.3c01023}},
year = {{2023}},
}