Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions
Skar-Gislinge, Nicholas ; Camerin, Fabrizio ; Stradner, Anna LU ; Zaccarelli, Emanuela and Schurtenberger, Peter LU
(2023)
In Molecular Pharmaceutics
20(5).
p.2738-2753
- Abstract
Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish a link between the microscopic molecular details and the resulting properties of an antibody solution through the characterization of clusters, which arise in the presence of self-associating antibodies. In particular, we find that experimental small-angle X-ray scattering data can be interpreted by means of analytical models previously... (More)
Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish a link between the microscopic molecular details and the resulting properties of an antibody solution through the characterization of clusters, which arise in the presence of self-associating antibodies. In particular, we find that experimental small-angle X-ray scattering data can be interpreted by means of analytical models previously exploited for the study of polymeric and colloidal objects, based on the presence of such clusters. The latter are determined by theoretical calculations and supported by computer simulations of a coarse-grained minimal model, in which antibodies are treated as Y-shaped colloidal molecules and attractive domains are designed as patches. Using the theoretically predicted cluster size distributions, we are able to describe the experimental structure factors over a wide range of concentration and salt conditions. We thus provide microscopic evidence for the well-established fact that the concentration-dependent increase in viscosity is originated by the presence of clusters. Our findings bring new insights on the self-assembly of monoclonal antibodies, which can be exploited for guiding the formulation of stable and effective antibody solutions.
(Less)
- author
- Skar-Gislinge, Nicholas
; Camerin, Fabrizio
; Stradner, Anna
LU
; Zaccarelli, Emanuela
and Schurtenberger, Peter
LU
- organization
- publishing date
- 2023-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antibodies, cluster theory, colloids, Monte Carlo simulations, patchy models, small-angle X-ray scattering
- in
- Molecular Pharmaceutics
- volume
- 20
- issue
- 5
- pages
- 16 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:37067466
- scopus:85154069525
- ISSN
- 1543-8384
- DOI
- 10.1021/acs.molpharmaceut.3c00191
- language
- English
- LU publication?
- yes
- id
- 02046f1b-0d59-478e-9e9d-4661505b85b9
- date added to LUP
- 2023-07-14 11:11:10
- date last changed
- 2024-04-19 23:26:55
@article{02046f1b-0d59-478e-9e9d-4661505b85b9,
abstract = {{<p>Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish a link between the microscopic molecular details and the resulting properties of an antibody solution through the characterization of clusters, which arise in the presence of self-associating antibodies. In particular, we find that experimental small-angle X-ray scattering data can be interpreted by means of analytical models previously exploited for the study of polymeric and colloidal objects, based on the presence of such clusters. The latter are determined by theoretical calculations and supported by computer simulations of a coarse-grained minimal model, in which antibodies are treated as Y-shaped colloidal molecules and attractive domains are designed as patches. Using the theoretically predicted cluster size distributions, we are able to describe the experimental structure factors over a wide range of concentration and salt conditions. We thus provide microscopic evidence for the well-established fact that the concentration-dependent increase in viscosity is originated by the presence of clusters. Our findings bring new insights on the self-assembly of monoclonal antibodies, which can be exploited for guiding the formulation of stable and effective antibody solutions.</p>}},
author = {{Skar-Gislinge, Nicholas and Camerin, Fabrizio and Stradner, Anna and Zaccarelli, Emanuela and Schurtenberger, Peter}},
issn = {{1543-8384}},
keywords = {{antibodies; cluster theory; colloids; Monte Carlo simulations; patchy models; small-angle X-ray scattering}},
language = {{eng}},
number = {{5}},
pages = {{2738--2753}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Molecular Pharmaceutics}},
title = {{Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions}},
url = {{http://dx.doi.org/10.1021/acs.molpharmaceut.3c00191}},
doi = {{10.1021/acs.molpharmaceut.3c00191}},
volume = {{20}},
year = {{2023}},
}