Spatial Positioning and Chemical Coupling in Coacervate‐in‐Proteinosome Protocells

Booth, Richard; Qiao, Yan; Li, Mei; Mann, Stephen

doi:10.1002/anie.201903756

Cited by 92 publications

(116 citation statements)

References 31 publications

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“…Furthermore, hybrid protocells of membrane‐free sub‐compartments within either water‐in‐oil (w/o) emulsions, giant vesicles or proteinosomes have been formed by spontaneous self‐assembly methods in bulk or by using microfluidic methodologies . In these systems, changes in temperature or osmotic pressure from the exterior of the lipid vesicles have led to phase separation of aqueous two phase systems and coacervates within the lipid vesicle.…”

Section: Introductionmentioning

confidence: 99%

Reversible pH‐Responsive Coacervate Formation in Lipid Vesicles Activates Dormant Enzymatic Reactions

et al. 2020

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In situ, reversible coacervate formation within lipid vesicles represents a key step in the development of responsive synthetic cellular models. Herein, we exploit the pH responsiveness of a polycation above and below its pKa, to drive liquid–liquid phase separation, to form single coacervate droplets within lipid vesicles. The process is completely reversible as coacervate droplets can be disassembled by increasing the pH above the pKa. We further show that pH‐triggered coacervation in the presence of low concentrations of enzymes activates dormant enzyme reactions by increasing the local concentration within the coacervate droplets and changing the local environment around the enzyme. In conclusion, this work establishes a tunable, pH responsive, enzymatically active multi‐compartment synthetic cell. The system is readily transferred into microfluidics, making it a robust model for addressing general questions in biology, such as the role of phase separation and its effect on enzymatic reactions using a bottom‐up synthetic biology approach.

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Section: Introductionmentioning

confidence: 99%

Reversible pH‐Responsive Coacervate Formation in Lipid Vesicles Activates Dormant Enzymatic Reactions

et al. 2020

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“…With the help of microfluidics, complex protocells where coacervates are enclosed in lipid vesicles, proteinosomes and hybrid vesicles have been fabricated, [236,245,254,257] the sequestration of proteins, enzymes, and substrates, [236,253,254] as well as metabolic cascade reactions in these protocells have been demonstrated. [233,245,258]…”

Section: Membraneless Coacervated Dropletsmentioning

confidence: 99%

Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

et al. 2020

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products of evolution over billions of years. They are featured by multiple hierarchical compartments performing specialized and exquisitely coordinated functions. The biological and genetic complexity of cells and subcellular components make understanding their physicochemical foundation piece by piece challenging. [1-5] Moreover, the mystery of how the very first cell, protocell, comes into exist in early earth scenario is unveiled yet. [6] Motivated by understanding protocell and biological cells, synthetic cells are being constructed. Started form the simplest form, aqueous droplet enclosed by a bilayer structure, researchers adopt a bottom-up approach to study machineries of biological cells, and explore possible forms of the protocell in early world conditions. [7] Synthetic cells are important to bridge the gap between cellular organism and nonliving matter. They refer to synthetic compartments that encapsulate a wide variety of molecules and mimic one or multiple cellular functions. By segregation of contents in different compartments, synthetic cells are now engineered to perform multiple processes and functions, including segregating genetic information, genetic circuits, protein synthesis, metabolism, growth, reproduce, recognition, intercellular crosstalk, and adaptivity to surroundings. [8-17] In these simplified cell models, cellular processes and signal pathways are reconstituted, providing insights for cell biology and offering new opportunities for designing smart cell-like carriers of therapeutics. [18-26] In addition, the hypothesis of "RNA world" has inspired the investigation of synthetic compartments as protocells, in which nucleotide permeation, compartmental division, the synthesis of macromolecular polynucleotide, and the polymerization of ribonucleic acids (RNA) are explored. [7,27,28] The beginning of synthesizing cell-like structures starts from amphiphiles self-assembled at liquid/liquid interfaces to form enclosed compartments. [29-32] Recently, techniques such as microfluidics facilitate the fabrication of complex compartments with high-order hierarchy with excellent control. [33-36] Formulations of compartmentalization can be diverse, there are reviews mainly focused on one particular type of synthetic compartments, such as lipid vesicles (liposomes), [22,30,37,38] polymer vesicles (polymersomes), [39-43] lipid-polymer hybrid Synthetic cells have a major role in gaining insight into the complex biological processes of living cells; they also give rise to a range of emerging applications from gene delivery to enzymatic nanoreactors. Living cells rely on compartmentalization to orchestrate reaction networks for specialized and coordinated functions. Principally, the compartmentalization has been an essential engineering theme in constructing cell-mimicking systems. Here, efforts to engineer liquid-liquid interfaces of multiphase systems into membrane-bounded and membraneless compartments, which include lipid vesicles, polymer vesicles, colloidosomes, hybrids, and coacervate droplets,...

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“…It has long been proposed that the first cells were membraneless droplets [18]. Accordingly, the investigation of interactions between these structures is an important endeavor [19][20][21] (Figure 3f ).…”

Section: Synthetic Tissuesmentioning

confidence: 99%

Synthetic tissues

Bayley

Hoskin

2019

Emerging Topics in Life Sciences

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While significant advances have been achieved with non-living synthetic cells built from the bottom-up, less progress has been made with the fabrication of synthetic tissues built from such cells. Synthetic tissues comprise patterned three-dimensional (3D) collections of communicating compartments. They can include both biological and synthetic parts and may incorporate features that do more than merely mimic nature. 3D-printed materials based on droplet-interface bilayers are the basis of the most advanced synthetic tissues and are being developed for several applications, including the controlled release of therapeutic agents and the repair of damaged organs. Current goals include the ability to manipulate synthetic tissues by remote signaling and the formation of hybrid structures with fabricated or natural living tissues.

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Spatial Positioning and Chemical Coupling in Coacervate‐in‐Proteinosome Protocells

Cited by 92 publications

References 31 publications

Reversible pH‐Responsive Coacervate Formation in Lipid Vesicles Activates Dormant Enzymatic Reactions

Reversible pH‐Responsive Coacervate Formation in Lipid Vesicles Activates Dormant Enzymatic Reactions

Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

Synthetic tissues

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