Abstract
Active coacervate droplets are liquid condensates coupled to a chemical reaction that turns over their components, keeping the droplets out of equilibrium. This turnover can be used to drive active processes such as growth, and provide an insight into the chemical requirements underlying (proto)cellular behaviour. Moreover, controlled growth is a key requirement to achieve population fitness and survival. Here we present a minimal, nucleotide-based coacervate model for active droplets, and report three key findings that make these droplets into evolvable protocells. First, we show that coacervate droplets form and grow by the fuel-driven synthesis of new coacervate material. Second, we find that these droplets do not undergo Ostwald ripening, which we attribute to the attractive electrostatic interactions and translational entropy within complex coacervates, active or passive. Finally, we show that the droplet growth rate reflects experimental conditions such as substrate, enzyme and protein concentration, and that a different droplet composition (addition of RNA) leads to altered growth rates and droplet fitness. These findings together make active coacervate droplets a powerful platform to mimic cellular growth at a single-droplet level, and to study fitness at a population level.
Highlights
Active coacervate droplets are liquid condensates coupled to a chemical reaction that turns over their components, keeping the droplets out of equilibrium
One of the simplest systems predicted to exhibit growth and division is a droplet coupled to a constant supply of droplet material or a chemical reaction: by keeping the reaction out of equilibrium, the droplet can sustain an active behaviour like growth[4,5,6,7,8,9]
Inspired by the phosphorylation-mediated liquid–liquid phase separation of peptides and RNA developed by the group of Keating[23], our group achieved reversible ATP-poly-L-lysine coacervates with the introduction of pyruvate kinase (PyK) to generate ATP in situ from ADP and phosphoenolpyruvate (PEP)[19]
Summary
Active coacervate droplets are liquid condensates coupled to a chemical reaction that turns over their components, keeping the droplets out of equilibrium. Modern cells rely on tightly coordinated mechanisms involving complex machinery, but the sustenance of life-like systems, from their origins to the emergence of a common ancestor, implies that primitive cells lacking similar specialized enzymes could already survive and perhaps even proliferate This suggests that the behaviour can be reproduced (and explained) using solely chemical principles[1,2]. As coacervate droplets are formed by liquid–liquid phase separation, they are in principle governed by the equilibrium concentrations of the building blocks, and when more material is supplied, the volume of the coacervate phase can grow while the overall internal concentration remains approximately constant This perfectly aligns with the active droplet requirements and is crucial given that most protocell models so far have increased in size via passive mechanisms: vesicle fusion[13], droplet coalescence and ripening[14,15], or uptake of externally added building blocks[16]. Under the same environmental conditions, droplets of different compositions grow at different rates, paving the way for the design of evolvable protocells
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