Coacervate‐Droplet Cased Synthetic Cells Regulated By Activated Carboxylic Acids (ACAs)

Regulating the formation and dissolution of active complex coacervate droplets with chemical reactions offers a powerful synthetic cell model. Such active droplets are also helpful in understanding the non-equilibrium nature of membrane-less organelles. Like many membrane-less organelles, these droplets rely on high-chemical potential reagents, like ATP, to maintain their transient nature. This study explores Activated Carboxylic Acids (ACAs) as a high-chemical potential fuel to modulate the lifetime of peptide-based coacervates through transient pH changes. We demonstrate that nitroacetic acid, a commonly used ACA, can effectively induce the formation and dissolution of coacervates by transiently altering the solution′s pH. The system, comprising the zwitterionic peptide Ac-FRGRGD-OH and polyanions, forms coacervates upon protonation at low pH and dissolves as the pH returns to neutral. Our findings indicate that the lifetime of these synthetic cells can be fine-tuned by varying the amount of ACA added, and the system can be refueled multiple times without significant interference from by-products. This ACA-driven reaction cycle is versatile, accommodating various coacervate compositions and enabling the uptake of diverse compounds, making it a valuable model for compartmentalization. The study underscores the potential of ACA-fueled coacervates as a platform for investigating biomolecular condensates and developing synthetic life systems.