title: Mechanochemical actuators of embryonic epithelial contractility.
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.
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213;
authors.forename: YongTae
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213;
authors.forename: Melis
authors.initials: M
authors.lastname: Hazar
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260;
authors.forename: Deepthi S
authors.initials: DS
authors.lastname: Vijayraghavan
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213;
authors.forename: Jiho
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260;
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Jackson
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260;
authors.forename: Sagar D
authors.initials: SD
authors.lastname: Joshi
authors.affiliation: 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.
authors.forename: William C
authors.initials: WC
authors.lastname: Messner
authors.affiliation: 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.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Davidson
authors.affiliation: 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.
authors.forename: Philip R
authors.initials: PR
authors.lastname: LeDuc
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D048430:Cell Shape / Q000187:drug effects*; D003911:Dextrans / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology; D046210:Microfluidic Analytical Techniques; D018613:Microscopy, Confocal; D012235:Rhodamines / Q000378:metabolism; D014982:Xenopus laevis; D015053:Zygote / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D003911:Dextrans; D007546:Isoquinolines; D012235:Rhodamines; C051311:rhodamine dextran; D000255:Adenosine Triphosphate; C017475:lucifer yellow
keywords: mechanotransduction; microfluidics; multicellular; signaling