Active coacervates driven by the waste-less formation and destruction of an unstable salt

Complex coacervates are liquid phases that form in water upon mixing two oppositely-charged polyelectrolytes and salt. Immediately upon mixing, the solution phase-separates through spinodal decomposition, resulting in a suspension of droplets in equilibrium with the surrounding water. The composition of coacervates is mostly aqueous (water 60-70% of their weight). but they concentrate most of the polyelectrolytes from the solution, making them relatively hydrophobic, and immiscible with the surrounding water. This composition gives coacervates unique properties, such as salt-responsiveness, or the ability to spontaneously sequester and compartmentalise organic molecules from solution.

Coacervate droplets have been used as responsive compartments for multiple applications: acting as drug delivery vehicles, microreactors, or protocells. One application that stands out is their use as mimics of membraneless organelles (MLOs), liquid droplets which play a role in several cellular processes - from gene expression to amyloid formation. MLOs and coacervates share many properties, but MLOs are active matter: they form transiently, move, disappear, and change properties over time. On the other hand, coacervates are typically equilibrium (or kinetically-trapped) structures. Current efforts to drive coacervates out-of-equilibrium rely on exergonic chemical reactions that modify one of the polyelectrolytes, and as such, are restricted to specific chemical functionalities. Furthermore, the accumulation of "waste"-products of the chemical reaction limits their applications over long periods of time.

Recently, our group has developed a novel methodology to drive complex coacervates out-of-equilibrium, driven by the decomposition of an unstable salt: ammonium carbonate. This salt spontaneously decomposes into ammonia and carbon dioxide, which in turn evaporate from the solution, decreasing the ionic strength. We have shown that this process can be used for time-triggered coacervate formation, and coacervates with time-dependent mechanical properties. Since our strategy targets the ionic strength of the solution and not the coacervate itself, it can be generalizable to multiple coacervate-forming systems with no synthetic effort. Furthermore, we have recently coupled this process to an enzymatic reaction that produces ammonium carbonate in-situ. By simultaneously producing and destroying ammonium carbonate, we can obtain coacervates with emergent behaviours, such as transient dissolution with tunable lifetimes. Furthermore, since the products of the reaction evaporate from the solution, no "waste" is accumulated and we can cycle between coacervate formation, transient dissolution, and aging an indefinite amount of times. This strategy can be used to better understand the properties of MLOs, or to develop new coacervate-based complex chemical systems.