Coacervation in systems chemistry

Compartmentalization within living cells is vital to orchestrate intracellular processes, but effective compartmentalization and organization within synthetic cells remains a key challenge. Here, the authors report a lab-on-a-chip system to reversibly trigger the formation of peptide-based coacervates as membraneless organelles via pH/temperature/osmolyte variations within cell-mimicking confinements.

Complex coacervation is propelled by the electrostatic association between oppositely charged polyelectrolytes, but the factors that drive complex coacervation have yet to be fully understood. Here, the authors investigate the influence of the backbone chemistry and ionic functional groups of five pairs of oppositely charged polyelectrolytes on complex coacervation.

Biomolecular condensates show distinct physicochemical properties that may affect the rate of enzymatic activity and control cellular redox reactions, however, their influence on the other types of chemical reaction remains underexplored. Here, the authors use reactive Martini simulations to probe the non-enzymatic macrocyclization reaction of benzene-1,3-dithiol in the presence of peptide condensates.

Artificial cells are promising models to study intercellular communications, however, the chemical communication between populations of artificial cells remains underexplored. Here, the authors show the exchange of proteins between distinct populations of coacervate-based artificial cells by regulation of protein affinity and competitive binding with hub protein 14-3-3.

Membranization of coacervate microdroplets can stabilize coacervates and enable the construction of hierarchical protocells by using various interfacial layers. Here, the authors demonstrate the modulation of interfacial membrane fluidity and thickness of dextran-bound coacervate protocells by adjusting the molecular weight of dextran or through enzymatic hydrolysis, achieving control over colloidal stability, interfacial molecular transport and cell-protocell interactions.

Biomolecular coacervates are emerging model systems to understand biological processes. Here, the authors reveal details on how the length and sequence of the DNA binders influence the multivalency-driven coacervate formation, how to introduce switching and autonomous behavior in reaction circuits, as well as how to engineer wetting, engulfment, and fusion in multi-coacervate system.

Peptide condensates are known to regulate compartmentalized enzymatic reactions, however, the influence of condensate chemical composition on enzymatic reactions is still poorly understood. Here, the authors study β-galactosidase as a simple enzymatic model and reveal that product formation is enhanced in heterotypic peptide-RNA condensates, but the reaction is restricted in homotypic peptide condensates.

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.