Control over membrane fluidity and biophysical properties of synthetic terpolymer stabilized complex coacervates†

Cell membranes are vital barriers that regulate the composition of the intracellular environment and facilitate communication processes essential for cellular function and survival. In comparison to lipid membranes, artificial polymeric membranes generally offer enhanced stability due to their higher molecular weight and greater variability in the nature of the macromolecular building blocks, which provides access to a broad chemistry toolbox to regulate important features such as fluidity and permeability. We recently developed an artificial cell platform based on a complex coacervate, in which a terpolymer, composed of a hydrophilic poly(ethylene glycol) segment, a hydrophobic poly(caprolactone-g-trimethylene carbonate) domain and a polyglutamate anchor (PEG-PCLgTMC-PGA) was used for stabilization. These membranized structures showed excellent permeability, due to the high fluidity of the membrane. However, the polymer membrane proved to be unselective with regard to the molecular weight of guest molecules that were exchanged with the environment. To advance this platform, a series of terpolymers with distinctive features were synthesized to further refine their regulatory features of the polymer membrane. Through investigation of structural terpolymer variants, including those in which the hydrophobic domain was based on PCLgTMC, poly(d,l-lactic acid) or polystyrene, their influence on membrane permeability, fluidity, and sequestration of hydrophobic molecules, such as cholesterol, was determined. With this extended range of membrane-forming building blocks, this coacervate platform is equipped with tailored permeability through interactions with the coacervate lumen and facilitates sequestration of hydrophobic molecules into the membrane and controlled fluidity.