Emergent Properties of Sticky Protein: In vitro studies on liquid protein

Biologists typically view proteins as discrete nanomachines dispersed in an aqueous environment. More recently however, cell biologists have begun to consider protein as a material, with biologically relevant microscopic properties. Under certain conditions some proteins condense out of their dispersed state via a process of liquid-liquid phase separation, to form liquid protein droplets. Due to their mechanism of formation, these dynamic liquid droplets benefit the cell by allowing for fast adaptive responses and spatiotemporal compartmentalisation of specific molecules to regulate biochemical reactions. Liquid protein has potential applications in synthetic biology and green chemistry. However, relationships between amino acid composition, material state, and selective partitioning of molecules to liquid protein are poorly understood. Our research aims to address these questions by starting with in vitro studies on a class of human proteins that facilitate subnuclear organisation via liquid-liquid phase separation (DBHS proteins). We have shown that we can produce these proteins recombinantly, and induce liquid droplet formation in vitro. Further studies using a variety of biophysical methods will aim to provide a knowledge base to direct the design of proteins with desired material characteristics, and better understand the effect of liquid protein on biochemical reactions.