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Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells

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Title: Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells
Authors: Hindley, JW
Zheleva, DG
Elani, Y
Charalambous, K
Barter, LMC
Booth, PJ
Bevan, CL
Law, RV
Ces, O
Item Type: Journal Article
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 multi-compartment-spanning designer pathways that can be utilised to control downstream events inside an artificial cell, leading to the assembly of micromachines capable of sensing and responding to changes in their local environment.
Issue Date: 20-Aug-2019
Date of Acceptance: 24-Jun-2019
URI: http://hdl.handle.net/10044/1/71675
DOI: 10.1073/pnas.1903500116
ISSN: 0027-8424
Publisher: National Academy of Sciences
Start Page: 16711
End Page: 16716
Journal / Book Title: Proceedings of the National Academy of Sciences
Volume: 116
Issue: 34
Copyright Statement: © 2019 Published under the PNAS license https://www.pnas.org/site/aboutpnas/licenses.xhtml.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/J017566/1
EP/K038648/1
EP/N016998/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
artificial cells
signaling pathway
nested vesicle
MscL
phospholipase A2
OPEN-CHANNEL STRUCTURE
ALPHA-HEMOLYSIN
COMMUNICATION
CALCIUM
VESICLES
MSCL
RECONSTITUTION
TRANSDUCTION
LIPOSOMES
ION
MscL
artificial cells
nested vesicle
phospholipase A2
signaling pathway
Artificial Cells
Calcium
Cell Communication
Cell Compartmentation
Chelating Agents
Escherichia coli Proteins
Ion Channels
Mechanotransduction, Cellular
Phospholipases A2
Calcium
Escherichia coli Proteins
Ion Channels
Chelating Agents
Cell Communication
Mechanotransduction, Cellular
Cell Compartmentation
Phospholipases A2
Artificial Cells
Publication Status: Published
Online Publication Date: 2019-08-01
Appears in Collections:Bioengineering
Department of Surgery and Cancer
Chemistry
Biological and Biophysical Chemistry
Chemical Engineering
Faculty of Medicine
Faculty of Natural Sciences
Faculty of Engineering