Mechanochemical actuators of embryonic epithelial contractility

YongTae Kim; Melis Hazar; Deepthi S. Vijayraghavan; Jiho Song; Timothy R. Jackson; Sagar D. Joshi; William C. Messner; Lance A. Davidson; Philip R. LeDuc

doi:10.1073/pnas.1405209111

Edited by Shu Chien, University of California, San Diego, La Jolla, CA, and approved August 18, 2014 (received for review March 20, 2014)

Significance

This study shows how cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. 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. Understanding the systems-level behavior of biological signaling networks may allow us to control biological actuators with engineered spatiotemporal stimulation. Our findings will provide a better understanding of contractility-dependent morphogenetic movements as well as the intercellular communication pathways critical during developmental biology, synthetic morphogenesis, and multicellular mechanotransduction signaling.

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.

Footnotes

↵¹Present address: The George W. Woodruff School of Mechanical Engineering, Wallace H. Coulter Department of Biomedical Engineering, Institute for Electronics and Nanotechnology, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
↵²Present address: American Air Liquide Inc., Delaware Research and Technology Center, Newark, DE 19702.
↵³Present address: Department of Mechanical Engineering, Tufts University, Medford, MA 02155.
↵⁴To whom correspondence may be addressed. Email: lad43{at}pitt.edu, william.messner{at}tufts.edu, or prl{at}andrew.cmu.edu.

Author contributions: Y.K., W.C.M., L.A.D., and P.R.L. designed research; Y.K., M.H., D.S.V., and J.S. performed research; Y.K., M.H., D.S.V., J.S., T.R.J., S.D.J., W.C.M., L.A.D., and P.R.L. contributed new reagents/analytic tools; Y.K., M.H., D.S.V., J.S., T.R.J., W.C.M., L.A.D., and P.R.L. analyzed data; S.D.J. and L.A.D. identified the use of extracellular ATP for inducing contractility in Xenopus embryonic tissues; and Y.K., W.C.M., L.A.D., and P.R.L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1405209111/-/DCSupplemental.