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Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells.


ABSTRACT: To date, reconstitution of one of the fundamental methods of cell communication, the signaling pathway, has been unaddressed in the bottom-up construction of artificial cells (ACs). Such developments are needed to increase the functionality and biomimicry of ACs, accelerating their translation and application in biotechnology. Here, we report the construction of a de novo synthetic signaling pathway in microscale nested vesicles. Vesicle-cell models respond to external calcium signals through activation of an intracellular interaction between phospholipase A2 and a mechanosensitive channel present in the internal membranes, triggering content mixing between compartments and controlling cell fluorescence. Emulsion-based approaches to AC construction are therefore shown to be ideal for the quick design and testing of new signaling networks and can readily include synthetic molecules difficult to introduce to biological cells. This work represents a foundation for the engineering of multicompartment-spanning designer pathways that can be utilized to control downstream events inside an AC, leading to the assembly of micromachines capable of sensing and responding to changes in their local environment.

SUBMITTER: Hindley JW 

PROVIDER: S-EPMC6708380 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells.

Hindley James W JW   Zheleva Daniela G DG   Elani Yuval Y   Charalambous Kalypso K   Barter Laura M C LMC   Booth Paula J PJ   Bevan Charlotte L CL   Law Robert V RV   Ces Oscar O  

Proceedings of the National Academy of Sciences of the United States of America 20190801 34


To date, reconstitution of one of the fundamental methods of cell communication, the signaling pathway, has been unaddressed in the bottom-up construction of artificial cells (ACs). Such developments are needed to increase the functionality and biomimicry of ACs, accelerating their translation and application in biotechnology. Here, we report the construction of a de novo synthetic signaling pathway in microscale nested vesicles. Vesicle-cell models respond to external calcium signals through ac  ...[more]

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