A colloid approach to self-assembling antibodies

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

Dithyrambus Quo Illustrissimo Stolbergae Comiti Carolo Ludovico Clementissime Regnanti Sacra Semisaecularia Ad D. XXI. Augusti MDCCCXI Rite A Civibus Celebrata / Gratulatur Johannes Christianus Benjaninus Rischelius Gymnasii Sangerhusani Rector

Vorlageform des Erscheinungsvermerks: Stolbergae Typis Schulzianis

Femtosecond x-ray crystallography

International audienceThis article gives an overview of recent x-ray diffraction experiments with time resolutions down to 10^-13s. The scientific motivation behind the development is outlined, using examples from solid state physics and biology. The ultrafast resolution may be provided either by fast detectors or short x-ray pulses, and the limitations of both techniques are discussed on the basis of state of the art experiments. In particular, it is shown that with present designs, high time resolution reduces the structural information attainable with high spatial resolution, thereby limiting feasible experiments on the ultrashort time-scale. The first experiment showing subpicosecond conformation changes was recently achieved with simple solids using an ultrafast laser-produced plasma x-ray source. The principles of this experiment are described in detail