ISS: Protein flow and gelation in the absence of solid-wall nucleation

Rensselaer Polytechnic Institute, Troy NY

Investigators

Abstract

Proteins are large, flexible macromolecules that perform a vast range of functions within living organisms, small and large. Their functions span from copying genetic material to providing structural integrity to cells and organisms. Because of their size, flexibility, and biochemistry, proteins can undergo structural changes that dictate their function, or sometimes cause disease. The ability to understand and predict how the conditions that proteins experience affect their structure and conformation, and in turn their functioning in solution, is very important. This award will be used for the development of predictive models for both fundamental science and industry, including development of first-principle models and manufacturing of pharmaceuticals. Microgravity makes it possible to study how protein solutions flow without complications associated with the interaction of protein solutions and solid walls. This project utilizes the microgravity environment of the International Space Station, where surface tension becomes a dominant force; this allows the study of protein solutions in the ring-sheared drop module, a container-less biochemical reactor. The purpose of this award is to gain deeper scientific understanding of protein association, aggregation, and gelation in systems with high protein concentration in the presence of free surfaces. The ring-sheared drop module aboard the International Space Station was designed for studying flows in gas-liquid systems, in which surface tension provides containment and shear is conveyed primarily through the action of surface shear viscosity. The ring-sheared drop is especially suitable for studying protein rheology as it minimizes any wall-nucleation effects. This project targets multiple classes of proteins, including globular, hormonal, and monoclonal antibody therapeutics. The recent development of protein solution viscosity models from first principles will be utilized as a foundation for mechanistic models including coupling of interfacial and bulk stresses to predict the flow of protein solutions. Variables captured by the model include the protein type (e.g., transport, hormone, or antibody), physical state (e.g. monomers, aggregates, fibrils, or gels), and concentration. Predictions from these models will be tested in the ring-sheared drop aboard the International Space Station. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.