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Abstract Compartments are a fundamental feature of life, based variously on lipid membranes, protein shells, or biopolymer phase separation. Here, this combines self‐assembling bacterial microcompartment (BMC) shell proteins and liquid‐liquid phase separation (LLPS) to develop new forms of compartmentalization. It is found that BMC shell proteins assemble at the liquid‐liquid interfaces between either 1) the dextran‐rich droplets and PEG‐rich continuous phase of a poly(ethyleneglycol)(PEG)/dextran aqueous two‐phase system, or 2) the polypeptide‐rich coacervate droplets and continuous dilute phase of a polylysine/polyaspartate complex coacervate system. Interfacial protein assemblies in the coacervate system are sensitive to the ratio of cationic to anionic polypeptides, consistent with electrostatically‐driven assembly. In both systems, interfacial protein assembly competes with aggregation, with protein concentration and polycation availability impacting coating. These two LLPS systems are then combined to form a three‐phase system wherein coacervate droplets are contained within dextran‐rich phase droplets. Interfacial localization of BMC hexameric shell proteins is tunable in a three‐phase system by changing the polyelectrolyte charge ratio. The tens‐of‐micron scale BMC shell protein‐coated droplets introduced here can accommodate bioactive cargo such as enzymes or RNA and represent a new synthetic cell strategy for organizing biomimetic functionality.
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Coacervation in polyzwitterion-polyelectrolyte systems and their potential applications for gastrointestinal drug delivery platforms
Abstract Traditionally, complex coacervation is regarded as a process whereby two oppositely charged polyelectrolytes self-assemble into spherical droplets. Here, we introduce the polyzwitterionic complex, “pZC”, formed by the liquid-liquid phase separation of a polyzwitterion and a polyelectrolyte, and elucidate a mechanism by which such complexes can assemble using theory and experimental evidence. This system exhibits orthogonal phase behavior-it remains intact in acidic conditions, but disassembles as the pH increases, a process governed by the acid-base equilibria of the constituent chains. We relate the observed phase behavior to physiological conditions within the gastrointestinal tract with a simulation of the gastroduodenal junction, and demonstrate using video microscopy the viability of polyzwitterionic coacervates as technologies for the pH-triggered release of cargo. Such a system is envisaged to tackle imminent problems of drug transport via the oral route and serve as a packaging solution to increase uptake efficiency.
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- Award ID(s):
- 1904660
- PAR ID:
- 10366454
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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