Speaker
Description
Protein-protein interactions are known to be often highly anisotropic due to the non-spherical protein shape and inhomogeneities in the distribution of charges and hydrophobic areas on the protein surface. The key static and dynamic properties of concentrated protein solutions and mixtures as those existing in the interior of living cells or used in pharmaceutical formulations are thus strongly dependent on solution parameters such as ionic strength, temperature and pH. Moreover, small variations in the protein structure caused for example by a single point mutation can change their solution behavior dramatically. Key examples are monoclonal antibodies (mAbs), i.e. Y-shaped proteins that have moved into the focus of pharmaceutical industry. While mAbs are central to modern therapeutics, their use is limited by formulation challenges such as high viscosity, aggregation, gelation, opalescence, and phase separation.
Electrostatic interactions fundamentally govern the structure, stability, and dynamics of antibody solutions, yet the impact of heterogeneous and anisotropic charge distributions on their behavior remains elusive. Here, we present results from a combination of scattering experiments, (micro)rheological measurements and simulations. We use a multiscale coarse-graining strategy to interpret data from different mAbs, which allows us to directly connect molecular-level electrostatics to collective solution properties. Our approach provides a predictive pathway to decode and control charge-driven interactions in complex biomolecules and, more generally, in heterogeneously-charged soft matter systems, with immediate relevance to protein formulation and biomaterials engineering.