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1. Mapping the phase behavior of coacervate-driven self-assembly in diblock copolyelectrolytes

   https://doi.org/10.1039/c9sm00741e  

   Ong, Gary M.; Sing, Charles E. (June 2019, Soft Matter)

   Oppositely-charged polymers can undergo an associative phase separation process known as complex coacervation, which is driven by the electrostatic attraction between the two polymer species. This driving force for phase separation can be harnessed to drive self-assembly, via pairs of block copolyelectrolytes with opposite charge and thus favorable coulombic interactions. There are few predictions of coacervate self-assembly phase behavior due to the wide variety of molecular and environmental parameters, along with fundamental theoretical challenges. In this paper, we use recent advances in coacervate theory to predict the solution-phase assembly of diblock polyelectrolyte pairs for a number of molecular design parameters (charged block fraction, polymer length). Phase diagrams show that self-assembly occurs at high polymer, low salt concentrations for a range of charge block fractions. We show that we qualitatively obtain limiting results seen in the experimental literature, including the emergence of a high polymer-fraction reentrant transition that gives rise to a self-compatibilized homopolymer coacervate behavior at the limit of high charge block fraction. In intermediate charge block fractions, we draw an analogy between the role of salt concentration in coacervation-driven assembly and the role of temperature in χ -driven assembly. We also explore salt partitioning between microphase separated domains in block copolyelectrolytes, with parallels to homopolyelectrolyte coacervation. 

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2. An explicit solvent model of coacervate structure and thermodynamics

   https://doi.org/10.1063/5.0305035  

   Alonso, Kayley; Baksi, Atanu; Knight, Isabel; Nguyen, Nga; Farshad, Mohsen; Srivastava, Samanvaya; Whitmer, Jonathan K (January 2026, The Journal of Chemical Physics)

   Complex coacervation, a liquid–liquid phase separation phenomenon driven by electrostatic interactions between oppositely charged polyelectrolytes (PEs), has attracted widespread attention because of its relevance in biological systems and potential applications in materials science. Although many theoretical models, experimental investigations, and computational studies have investigated the thermodynamics, phase coexistence behavior, and rheological properties in great detail, a molecular-level understanding of the internal structure of the complex coacervate phase is still lacking. In this study, we investigate the effects of the degree of polymerization of the polyelectrolytes (N) on the phase behavior and internal structure of the resulting coacervate phase using molecular dynamics simulations employing a simplistic bead–spring model of polyelectrolytes and explicit nonpolar solvents. Our simulations show an increase in coacervate phase stability with N, elevating the critical temperature in agreement with existing theoretical predictions and experimental observations. The polyelectrolytes inside the dense phase maintain a homogeneous overlapping distribution without collapsing into globules. The compactness of the dense phase increases with N in agreement with prior experimental observations, despite a concomitant increase in the polymer’s effective size as quantified by its radius of gyration (Rg). We discuss the implications of this model for a fundamental understanding of the coacervation process and as a first step toward the systematic examination of the mutual role of electrostatics and chemistry in the behavior of solvated polyions. 

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3. Coacervation of poly-electrolytes in the presence of lipid bilayers: mutual alteration of structure and morphology

   https://doi.org/10.1039/D2SC02013K  

   Mondal, Sayantan; Cui, Qiang (July 2022, Chemical Science)

   Many intrinsically disordered peptides have been shown to undergo liquid–liquid phase separation and form complex coacervates, which play various regulatory roles in the cell. Recent experimental studies found that such phase separation processes may also occur at the lipid membrane surface and help organize biomolecules during signaling events; in some cases, phase separation of proteins at the membrane surface was also observed to lead to significant remodeling of the membrane morphology. The molecular mechanisms that govern the interactions between complex coacervates and lipid membranes and the impacts of such interactions on their structure and morphology, however, remain unclear. Here we study the coacervation of poly-glutamate (E 30 ) and poly-lysine (K 30 ) in the presence of lipid bilayers of different compositions. We carry out explicit-solvent coarse-grained molecular dynamics simulations by using the MARTINI (v3.0) force-field. We find that more than 20% anionic lipids are required for the coacervate to form stable contact with the bilayer. Upon wetting, the coacervate induces negative curvature to the bilayer and facilitates local lipid demixing, without any peptide insertion. The magnitude of negative curvature, extent of lipid demixing, and asphericity of the coacervate increase with the concentration of anionic lipids. Overall, we observe a decrease in the number of contacts among the polyelectrolytes as the droplet spreads over the bilayer. Therefore, unlike previous suggestions, interactions among polyelectrolytes do not constitute a driving force for the membrane bending upon wetting by the coacervate. Rather, analysis of interaction energy components suggests that bending of the membrane is favored by enhanced interactions between polyelectrolytes with lipids as well as with counterions. Kinetic studies reveal that, at the studied polyelectrolyte concentrations, the coacervate formation precedes bilayer wetting. 

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4. Recent progress in the science of complex coacervation

   https://doi.org/10.1039/D0SM00001A  

   Sing, Charles E.; Perry, Sarah L. (March 2020, Soft Matter)

   Complex coacervation is an associative, liquid–liquid phase separation that can occur in solutions of oppositely-charged macromolecular species, such as proteins, polymers, and colloids. This process results in a coacervate phase, which is a dense mix of the oppositely-charged components, and a supernatant phase, which is primarily devoid of these same species. First observed almost a century ago, coacervates have since found relevance in a wide range of applications; they are used in personal care and food products, cutting edge biotechnology, and as a motif for materials design and self-assembly. There has recently been a renaissance in our understanding of this important class of material phenomena, bringing the science of coacervation to the forefront of polymer and colloid science, biophysics, and industrial materials design. In this review, we describe the emergence of a number of these new research directions, specifically in the context of polymer–polymer complex coacervates, which are inspired by a number of key physical and chemical insights and driven by a diverse range of experimental, theoretical, and computational approaches. 

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5. Tuning chain interaction entropy in complex coacervation using polymer stiffness, architecture, and salt valency

   https://doi.org/10.1039/c7me00108h  

   Lytle, Tyler K.; Sing, Charles E. (January 2018, Molecular Systems Design & Engineering)

   Oppositely-charged polyelectrolytes can undergo a liquid–liquid phase separation in a salt solution, resulting in a polymer-dense ‘coacervate’ phase that has found use in a wide range of applications from food science to self-assembled materials. Coacervates can be tuned for specific applications by varying parameters such as salt concentration and valency, polyelectrolyte length, and polyelectrolyte identity. Recent simulation and theory has begun to clarify the role of molecular structure on coacervation phase behavior, especially for common synthetic polyelectrolytes that exhibit high charge densities. In this manuscript, we use a combination of transfer matrix theory and Monte Carlo simulation to understand at a physical level how a range of molecular features, in particular polymer architecture and stiffness, and salt valency can be used to design the phase diagrams of these materials. We demonstrate a physical picture of how the underlying entropy-driven process of complex coacervation is affected by this wide range of physical attributes. 

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