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Self-Interactions of Two Monoclonal Antibodies : Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling

Mahapatra, Sujata ; Polimeni, Marco LU ; Gentiluomo, Lorenzo ; Roessner, Dierk ; Frieß, Wolfgang ; Peters, Günther H. J. ; Streicher, Werner W. ; Lund, Mikael LU orcid and Harris, Pernille (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.

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author
; ; ; ; ; ; ; and
organization
publishing date
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}},
}