A colloid approach to self-assembling antibodies
July 14-17, 2019
Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations, yet their tendency to aggregate and the resulting high viscosity pose considerable problems. Here we tackle this problem by a soft condensed matter physics approach which combines a variety of experimental measurements with a patchy colloid model, amenable of analytical solution. We thus report results of antibodies structural and dynamic properties obtained through scattering methods and microrheological experiments. 1 We model the data using a colloid-inspired approach, explicitly taking into account both the anisotropic shape of the molecule and their charge distribution. Our simple patchy model is able to disentangle self-assembly and intermolecular interactions, and to quantitatively describe the concentration dependence of the osmotic compressibility, collective diffusion coefficient and zero shear viscosity. Our results offer new insights on the key problem of antibody formulations providing a theoretical and experimental framework for a quantitative assessment of the effects of additional excipients or chemical modifications and a prediction of the resulting viscosity.
1) Nicholas Skar-Gislinge, Michela Ronti, Tommy Garting, Christian Rischel, Peter Schurtenberger, Emanuela Zaccarelli, and Anna Stradner, Molecular Pharm. (2019, submitted)
Peter Schurtenberger, "A colloid approach to self-assembling antibodies" in "Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties", Samiul Amin, Manhattan College, USA Miguel Rodrigues, University of Lisbon, Portugal Paolo Arosio, ETHZ, Switzerland Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/bpcf_iii/30