(305e) Thermodynamics and Transport Properties of Fluids with Intermediate Range Order with Application to Protein Solutions and Biopharmaceuticals
The glass transition of colloidal dispersions interacting with both a short-ranged attraction and long-ranged repulsion is studied using highly purified lysozyme solutions. Newtonian liquid behavior is observed at all conditions while measurements of the dynamics in the short-time limit show features typical of glassy colloidal systems at high protein concentrations. This interesting behavior is due to the competition of the attraction and repulsion that produces a heterogeneous microstructure only at intermediate range length scales. The results demonstrate that theories for the macroscopic properties of systems with competing interactions need to include intermediate range order. (Phys. Rev. Lett. 2015)
Recently, reversible cluster formation has been identified as an underlying cause of anomalously large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations, which poses a major challenge to the use of subcutaneous injection for some mAbs. A fundamental understanding of the structural and dynamic origins of high viscosities in concentrated mAb solutions is thus of significant relevance to mAb applications in human health care as well as of scientific interests. Here, we present a detailed investigation of an IgG1 based mAb to relate the short time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. The combination of light scattering, small angle neutron scattering and neutron spin echo measurement techniques conclusively demonstrates that, upon adding Na2SO4, these antibodies form strongly bounded reversible dimers at dilute concentrations, which interact with each other to form loosely bounded, large, transient clusters when concentrated. This hierarchical structure formation in solution causes a significant increase in the solution viscosity. (J. Chem. Phys. B, 2015)
Finally, simulations and theory have been performed to explore the dynamics of colloids with intermediate range order. The results are compared with recent experiments on globular proteins. The dynamical signatures of intermediate range order and cluster formation are presented and discussed.