Tuning the physicochemical properties of rationally designed protein-based biomolecular condensates

Biomolecular condensates form through liquid–liquid phase-separation of multivalent biomolecules, enabling the spatiotemporal control of biochemical processes within the cellular environment. They can selectively partition different components, maintain ionic gradients, and form/dissolve spontaneously in feedback loops, all without the need for a membrane or energy expenditure. Within the cell, the composition, size, localisation and rheology can tune these biomolecular condensates to perform specific biological functions; however, how this happens is not fully understood. Rationally designed biomolecular condensates provide a “bottom-up approach” towards gaining molecular-level insights into what makes condensates optimal for their biological roles. In this review, we discuss how engineered protein condensates outline emerging relationships between design parameters and physicochemical tuneability, and how these systems may be adapted for biological applications.