pH-responsive regulation of multiphase coacervate wetting via phase selective enrichment of fatty acids

Biomolecular condensates with multiphasic architectures organize specific biomolecular processes in different compartments and dynamically reconfigure their structure to regulate their biological functions. Here, we employ multiphase coacervates as model condensates to illustrate pH-responsive dynamic reconfiguration of multiphase wetting interactions mediated by phase selective enrichment of fatty acids. We noted that unsaturated fatty acids such as linolenic acid (LA) can enrich within specific coacervates, via spontaneous substitution of like charged coacervate components, to drastically alter coacervate properties such as viscosity and surface tension. By selectively enriching fatty acids within the outer phase of a multiphase coacervate, the changes in coacervate properties were used to trigger the outer phase to dewet the inner phase and separate into two droplets. Dynamic switching between wetting and dewetting states of multiphase droplets was achieved by adjusting the outer phase composition via pH changes, which impacted LA's ability to substitute coacervate components. Finally, chemical signaling mediated reconfiguration of coacervate-based synthetic cells was shown using urease containing microgels, which secreted pH-based chemical signals to propagate a reconfiguration front within multiphase droplet populations. Taken together, our results highlight opportunities for the design of dynamically reconfigurable synthetic cells capable of transducing chemical signals into morphological changes and suggest that lipids enriched within condensates may be involved in regulating their morphology and function.