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Photo Mikael Lund

Mikael Lund

Professor

Photo Mikael Lund

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

Author

  • Sujata Mahapatra
  • Marco Polimeni
  • Lorenzo Gentiluomo
  • Dierk Roessner
  • Wolfgang Frieß
  • Günther H. J. Peters
  • Werner W. Streicher
  • Mikael Lund
  • Pernille Harris

Summary, in English

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.

Department/s

  • Computational Chemistry
  • eSSENCE: The e-Science Collaboration
  • LINXS - Institute of advanced Neutron and X-ray Science

Publishing year

2022

Language

English

Pages

508-519

Publication/Series

Molecular Pharmaceutics

Volume

19

Issue

2

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Physical Chemistry (including Surface- and Colloid Chemistry)

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1543-8384