Engineering Membrane-Less, Protein-Rich Organelles

Compartmentalization of biochemical processes is a critical form of regulation in natural signaling and metabolic pathways. We are designing synthetic protein scaffolds built by tethering modular protein-protein interactions domains to form programmable complexes. Through the use of multivalent interactions, protein-rich complexes sufficiently dense to phase separate into a gel, thereby providing potential as a designable, membrane-less organelle. We are investigating the ability to controllably partition desired proteins and metabolites inside or outside of the droplet. We hope to gain the ability to program these droplets to sequester desired substrates, while excluding undesired proteins and metabolites.