Programmable Coacervate Droplets via Reaction-Coupled Liquid-Liquid Phase Separation (LLPS) and Competitive...

Area of Science:

• Biochemistry and Materials Science
• Supramolecular Chemistry
• Chemical Biology

Background:

• Membraneless biomolecular condensates regulate biological functions via liquid-liquid phase separation (LLPS).
• Synthetic coacervate droplets are emerging as tools to mimic and study LLPS.
• Programmable coacervates offer spatiotemporal control over synthetic liquid phases.

Purpose of the Study:

• To demonstrate programming of LLPS in synthetic systems using competitive binding and reaction-coupled assembly.
• To develop a coacervation mechanism distinct from complex coacervates, utilizing small building blocks.
• To achieve temporal control over coacervation through dynamic covalent chemistry.

Main Methods:

• Utilized dynamic covalent bonds (boronate esters) and small chromophoric building blocks with boronic acid groups.
• Employed monosaccharides as substrates to trigger coacervation via reaction-coupled assembly.
• Applied spectroscopic probing, kinetic analyses, and confocal microscopy for mechanistic insights and visualization.

Main Results:

• Demonstrated reaction-driven, temporally controlled LLPS using a "sticker-and-spacer" coacervation mechanism.
• Showcased competitive binding-driven control over coacervation growth, inhibition, and dissolution, influenced by monosaccharide reactivity.
• Revealed glucose-selective coacervation and transient phase separation via pH modulation.

Conclusions:

• Developed a novel strategy for programmable liquid-liquid phase separation (LLPS) using dynamic covalent chemistry and small molecules.
• The approach offers spatiotemporal control over synthetic coacervates, mimicking biological condensate behavior.
• This work provides a platform for designing coacervate droplets with tunable, biorelevant emergent properties.