KINETIC EVOLUTION OF STABLE AND METASTABLE STATES OF PROTEIN SOLUTIONS

摘要

The thermodynamic and kinetic properties of protein solutions are important in many industrial, scientific and pathophysiological applications. These applications include the large scale separation of proteins by aqueous two phase partition and the production of crystals of biologically important proteins for the determination of their three-dimensional structure. Protein solutions exhibit phase transformations such as crystallization, metastable liquid-liquid phase separation, aggregation, self assembly and gelation. We have investigated the crystallization and metastable liquid-liquid phase separation (LLPS) in the gamma crystallins, a family of proteins of eye lenses. In crystallization, a solid (crystal) forms from the protein solution. In LLPS, the solution separates into two coexisting liquid phases of unequal protein concentration. This LLPS is brought about by the attractive interactions between the gamma crystallins. Although LLPS is metastable with respect to crystallization, crystal formation in the gamma crystallins is usually slow enough so that the coexistence curve can still be measured. We have analyzed the effect of protein modifications (genetic mutations) and the effect of additives (PEG) on the phase behavior of gamma crystallins aqueous solutions.