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Artificial morphogen-mediated differentiation in synthetic protocells.

ABSTRACT: The design and assembly of artificial protocell consortia displaying dynamical behaviours and systems-based properties are emerging challenges in bottom-up synthetic biology. Cellular processes such as morphogenesis and differentiation rely in part on reaction-diffusion gradients, and the ability to mimic rudimentary aspects of these non-equilibrium processes in communities of artificial cells could provide a step to life-like systems capable of complex spatiotemporal transformations. Here we expose acoustically formed arrays of initially identical coacervate micro-droplets to uni-directional or counter-directional reaction-diffusion gradients of artificial morphogens to induce morphological differentiation and spatial patterning in single populations of model protocells. Dynamic reconfiguration of the droplets in the morphogen gradients produces a diversity of membrane-bounded vesicles that are spontaneously segregated into multimodal populations with differentiated enzyme activities. Our results highlight the opportunities for constructing protocell arrays with graded structure and functionality and provide a step towards the development of artificial cell platforms capable of multiple operations.

SUBMITTER: Tian L

PROVIDER: S-EPMC6658542 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Artificial morphogen-mediated differentiation in synthetic protocells.

Tian Liangfei L Li Mei M Patil Avinash J AJ Drinkwater Bruce W BW Mann Stephen S

Nature communications 20190725 1

The design and assembly of artificial protocell consortia displaying dynamical behaviours and systems-based properties are emerging challenges in bottom-up synthetic biology. Cellular processes such as morphogenesis and differentiation rely in part on reaction-diffusion gradients, and the ability to mimic rudimentary aspects of these non-equilibrium processes in communities of artificial cells could provide a step to life-like systems capable of complex spatiotemporal transformations. Here we ex ...[more]

PMID: 31346180

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Project description:BackgroundProtocell refers to the basic unit of life and synthetic molecular assembly with cell structure and function. The protocells have great applications in the field of biomedical technology. Simulating the morphology and function of cells is the key to the preparation of protocells. However, some organic solvents used in the preparation process of protocells would damage the function of the bioactive substance. Perfluorocarbon, which has no toxic effect on bioactive substances, is an ideal solvent for protocell preparation. However, perfluorocarbon cannot be emulsified with water because of its inertia.MethodsSpheroids can be formed in nature even without emulsification, since liquid can reshape the morphology of the solid phase through the scouring action, even if there is no stable interface between the two phases. Inspired by the formation of natural spheroids such as pebbles, we developed non-interfacial self-assembly (NISA) of microdroplets as a step toward synthetic protocells, in which the inert perfluorocarbon was utilized to reshape the hydrogel through the scouring action.ResultsThe synthetic protocells were successfully obtained by using NISA-based protocell techniques, with the morphology very similar to native cells. Then we simulated the cell transcription process in the synthetic protocell and used the protocell as an mRNA carrier to transfect 293T cells. The results showed that protocells delivered mRNAs, and successfully expressed proteins in 293T cells. Further, we used the NISA method to fabricate an artificial cell by extracting and reassembling the membrane, proteins, and genomes of ovarian cancer cells. The results showed that the recombination of tumor cells was successfully achieved with similar morphology as tumor cells. In addition, the synthetic protocell prepared by the NISA method was used to reverse cancer chemoresistance by restoring cellular calcium homeostasis, which verified the application value of the synthetic protocell as a drug carrier.ConclusionThis synthetic protocell fabricated by the NISA method simulates the occurrence and development process of primitive life, which has great potential application value in mRNA vaccine, cancer immunotherapy, and drug delivery.

Dataset Information

Artificial morphogen-mediated differentiation in synthetic protocells.

Publications

Artificial morphogen-mediated differentiation in synthetic protocells.

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