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Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14366-71. doi: 10.1073/pnas.1405209111. Epub 2014 Sep 22.

Mechanochemical actuators of embryonic epithelial contractility.

Author information

1
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213;
2
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260;
3
Departments of Mechanical Engineering and Electrical and Computer Engineering and Robotics Institute, Carnegie Mellon University, Pittsburgh, PA 15213; lad43@pitt.edu william.messner@tufts.edu prl@andrew.cmu.edu.
4
Departments of Bioengineering, Developmental Biology, and Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15260; and lad43@pitt.edu william.messner@tufts.edu prl@andrew.cmu.edu.
5
Departments of Mechanical Engineering, Biomedical Engineering, Computational Biology, and Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213 lad43@pitt.edu william.messner@tufts.edu prl@andrew.cmu.edu.

Abstract

Spatiotemporal regulation of cell contractility coordinates cell shape change to construct tissue architecture and ultimately directs the morphology and function of the organism. Here we show that contractility responses to spatially and temporally controlled chemical stimuli depend much more strongly on intercellular mechanical connections than on biochemical cues in both stimulated tissues and adjacent cells. We investigate how the cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. Our custom microfluidic control system allows spatiotemporally controlled stimulation with extracellular ATP, which results in locally distinct contractility followed by mechanical strain pattern formation. The stimulation-response circuit exposed here provides a better understanding of how morphogenetic processes integrate responses to stimulation and how intercellular responses are transmitted across multiple cells. These findings may enable one to create a biological actuator that actively drives morphogenesis.

KEYWORDS:

mechanotransduction; microfluidics; multicellular; signaling

PMID:
25246549
PMCID:
PMC4210000
DOI:
10.1073/pnas.1405209111
[Indexed for MEDLINE]
Free PMC Article

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