One-Step Generation of Cell-Encapsulating Compartments via Polyelectrolyte Complexation in an Aqueous Two Phase System.

Abstract

Diverse fields including drug and gene delivery and live cell encapsulation require biologically compatible encapsulation systems. One widely adopted means of forming capsules exploits cargo-filled microdroplets in an external, immiscible liquid phase that are encapsulated by a membrane that forms by trapping of molecules or particles at the drop surface, facilitated by the interfacial tension. To eliminate the potentially deleterious oil phase often present in such processes, we exploit the aqueous two phase system of poly(ethylene glycol) (PEG) and dextran. We form capsules by placing dextran-rich microdroplets in an external PEG-rich phase. Strong polyelectrolytes present in either phase form complexes at the drop interface, thereby forming a membrane encapsulating the fluid interior. This process requires considerable finesse as both polyelectrolytes are soluble in either the drop or external phase, and the extremely low interfacial tension is too weak to provide a strong adsorption site for these molecules. The key to obtaining microcapsules is to tune the relative fluxes of the two polyelectrolytes so that they meet and complex at the interface. We identify conditions for which complexation can occur inside or outside of the drop phase, resulting in microparticles or poor encapsulation, respectively, or when properly balanced, at the interface, resulting in microcapsules. The resulting microcapsules respond to the stimuli of added salts or changes in osmotic pressure, allowing perturbation of capsule permeability or triggered release of capsule contents. We demonstrate that living cells can be sequestered and interrogated by encapsulating Pseudomonas aeruginosa PAO1 and using a Live/Dead assay to assess their viability. This method paves the way to the formation of a broad variety of versatile functional membranes around all aqueous capsules; by tuning the fluxes of complexing species to interact at the interface, membranes comprising other complexing functional moieties can be formed.