Steering Coacervation by a Pair of Broad-Spectrum Regulators

Coacervation is liquid-liquid phase separation ubiquitous in industrial applications and cellular biology. Inspired by cellular manipulation of coacervate droplets such as P granules, we report here a regulatory strategy to manipulate synthetic coacervation in a spatiotemporally controllable manner. Two oppositely charged small molecules are shown to phase separate into coacervate droplets in water as a result of electrostatic attraction, hydrophobic effect, and entropy. We identify a down regulator, β-cyclodextrin, to disrupt the hydrophobic effect, thus dissolving the droplets, and an up regulator, amylase, to decompose β-cyclodextrin, thus restoring the droplets. The regulation kinetics is followed in real time on a single-droplet level, revealing diffusion-limited dissolution and reaction-limited condensation, respectively, taking ∼4 s and 2-3 min. Versatility of this strategy to manipulate the coacervation is demonstrated in two aspects: spatially distributed coacervation in virtue of amylase-grafted hydrogel frameworks and coacervate transportation across membranes and hydrogel networks via a disassemble-to-pass strategy. The current regulatory pairs and strategies are anticipated to be general for a wide variety of synthetic self-assembly systems.