(55g) Organizing Biochemical Reactions with Protein Droplets

Eukaryotic cells organize complex biochemistry by segregating reactions into functional compartments called organelles. Some of them, such as the nucleus and mitochondria, are bounded by membranes. But many others, like nucleoli, stress granules, P bodies, Cajal bodies, and signaling complexes, do not have membranes. Recent studies show that those membrane-free organelles are liquid droplets condensed from the cytoplasm, following the principles of liquid-liquid demixing. Long before the discovery that cells use liquid-liquid demixing to create membrane-free organelles, polymer-rich droplets were observed in lyophilic colloids and were termed as coacervate. Coacervates have been used as models for protocells, as soft materials, as reactors to increase reaction rates, and as delivery vehicles for proteins and small molecules. Protein-based droplets offer high biocompatibility and easy manipulation, are more advantageous than conventional coacervates and therefore have the potential to be used in many bioprocesses. Drawing on my experiences in soft matter and cell biology, I have been employing multidisciplinary tools including genetic manipulation, live cell imaging, biochemical reconstitution, optogenetic tools, microrheology, and fluorescence correlation spectroscopy to understand how intramolecular interactions drive liquid-liquid demixing, control droplet properties and determine specificity in cellular functions, which will continue to be one of my research directions. In parallel, I will take advantage of my training in biochemical engineering to design protein droplet-based bioprocesses including bioreactors in vitro and synthetic organelles in cells to increase reaction rates and product yields of pharmaceutically important molecules.