  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 solution viscosity has posed
considerable problems. It remains a very difficult task to understand and
predict the phase behavior and stability of such solutions. Here we present a
systematic study of the concentration dependence of the structural and dynamic
properties of monoclonal antibodies using a combination of different scattering
methods and microrheological experiments. To interpret these data, we use a
colloid-inspired approach based on a simple patchy model, which explicitly
takes into account the anisotropic shape and the charge distribution of the
molecules. Combining theory, simulations and experiments, we are able to
disentangle self-assembly and intermolecular interactions and to quantitatively
describe the concentration dependence of structural and dynamic quantities such
as the osmotic compressibility, the collective diffusion coefficient and the
zero shear viscosity over the entire range of investigated concentrations. This
simple patchy model not only allows us to consistently describe the
thermodynamic and dynamic behavior of mAb solutions, but also provides a robust
estimate of the attraction between their binding sites. It will thus be an
ideal starting point for future work on antibody formulations, as it provides a
quantitative assessment of the effects of additional excipients or chemical
modifications on antibody interactions, and a prediction of their effect on
solution viscosity.
