Concentrated antibody solutions: bridging structure and viscosity

In the realm of biomolecules, monoclonal antibodies have proven to be highly effective for the treatment of various diseases thanks to their high specificity. On the other hand, they typically present high viscosities in concentrated solutions, which dramatically alters their flow and dynamical properties and limits their suitability as self-injectable and safe biologics. Currently, a univocal framework providing microscopic interpretation to the enhanced viscosity is missing, while it has been observed that an approach inspired by polymers and colloidal physics can bring remarkable insights in this regard.



I will thus show that a meaningful description of the collective behavior of antibodies must consider the specificities of their anisotropic shape and charge, mapped from the all-atom representation into a coarse-grained modeling. By directly calculating static and dynamical descriptors of the system and comparing to experiments, we tie the microscopic peculiarities of the antibody to the macroscopic response by providing evidence of the link between the formation of transient clusters in solution and the arising viscosity behavior. These findings are essential for developing novel drug formulations and for engineering individual molecules with desired solution properties.