Coacervation in systems chemistry

Dynamic microscale droplets produced by liquid–liquid phase separation (LLPS) have emerged as appealing biomaterials, but their instability hinders their assembly into high-order structures with collective behaviors. Here, the authors review current strategies for stabilizing droplets, as well as recent developments in the applications of such LLPS droplets, and provide insights into how stabilized droplets can self-assemble into higher-order structures that display coordinated functions.

Fluorescence-based oligonucleotide probes, also known as molecular beacons (MBs), are popular for detecting nucleic acids with high specificity. Here, the authors demonstrate self-sequestration of MB-based biosensors and target strands within peptide-based coacervates, increasing local concentrations and significantly increasing the sensitivity and kinetics of the DNA biosensors.

Peptide-based coacervates display interesting properties for biomedical applications, however, the link between peptide structure and coacervate material properties remains unclear. Here, the authors report a direct correlation between the primary and secondary structures of the peptides and the viscoelastic properties of the coacervates.

Therapeutic proteins have great potential for the treatment of various diseases, however, achieving high delivery efficiency remains challenging. Here, the authors develop a complex coacervate system formed via the phase separation of anionic metabolite NADPH with a short arginine-rich peptide, and apply it to the redox-responsive drug delivery of therapeutic proteins.

Self-reproducing autocatalytic chemical reaction networks have the potential to demonstrate heritability and evolvability, however, achieving functional catalytic assembly and reaction networks within a phase-separated environment remains challenging. Here, the authors report multispecies chemical reaction networks of self-producing RNAs within charge-rich coacervates.

Liquid-liquid phase separation (LLPS) underlies the formation of intracellular membraneless compartments in biology and may have played a role in the formation of protocells that concentrate key chemicals during the origins of life. While LLPS of simple systems, such as oil and water, is well understood, many aspects of LLPS in complex, out-of-equilibrium molecular systems remain elusive. Here, the author discusses open questions and recent insights related to the formation, function and fate of such condensates both in cell biology and protocell research.

Synthetic models of cells are becoming increasingly sophisticated, but engineering communication between these and living cells remains challenging. Here the authors review modes of communication and signal processing between living cells and synthetic analogs, such as giant unilamellar vesicles, proteinosomes, and coacervates.