Experimental control of excitable embryonic tissues: three stimuli induce rapid epithelial contraction

During embryonic development and wound healing, the mechanical signals transmitted from cells to their neighbors induce tissue rearrangement and directional movements. It has been observed that forces exerted between cells in a developing tissue under stress are not always monotonically varying, but they can be pulsatile. Here we investigate the response of model tissues to controlled external stresses. Spherical cellular aggregates are subjected to one-dimensional stretching forces using micropipette aspiration. At large enough pressures, the aggregate flows smoothly inside the pipette. However, in a narrow range of moderate aspiration pressures, the aggregate responds by pulsed contractions or “shivering.” We explain the emergence of this shivering behavior by means of a simple analytical model where the uniaxially stretched cells are represented by a string of Kelvin–Voigt elements. Beyond a deformation threshold, cells contract and pull on neighboring cells after a time delay for cell response. Such an active behavior has previously been found to cause tissue pulsation during dorsal closure of Drosophila embryo.

Section: Discussionsupporting

confidence: 66%

Mechanosensitive shivering of model tissues under controlled aspiration

Guevorkian

Gonzalez‐Rodriguez

Carlier

et al. 2011

“…The time constant for the recoil (Fig. 2E) was of order 5 min (Table 1), similar to time constants for contraction of gastrula epithelium subjected to nonspecific stimuli (23). If true elastic deformation were involved, a spring-like stretching of some structural component of the cell would have to be maintained over hours and through cell divisions.…”

Section: Resultssupporting

confidence: 59%

Large-scale mechanical properties of Xenopus embryonic epithelium

Luu

David

Ninomiya

et al. 2011

Epithelia are planar tissues that undergo major morphogenetic movements during development. These movements must work in the context of the mechanical properties of epithelia. Surprisingly little is known about these mechanical properties at the time and length scales of morphogenetic processes. We show that at a time scale of hours, Xenopus gastrula ectodermal epithelium mimics an elastic solid when stretched isometrically; strikingly, its area increases twofold in the embryo by such pseudoelastic expansion. At the same time, the basal side of the epithelium behaves like a liquid and exhibits tissue surface tension that minimizes its exposed area. We measure epithelial stiffness (∼1 mN/m), surface tension (∼0.6 mJ/m 2 ), and epithelium-mesenchyme interfacial tensions and relate these to the folding of isolated epithelia and to the extent of epithelial spreading on various tissues. We propose that pseudoelasticity and tissue surface tension are main determinants of epithelial behavior at the scale of morphogenetic processes.

“…This timescale for this contraction response is comparable to the timescales reported previously for mechanical or biochemical signal transmission. Whereas a few seconds or milliseconds have been reported in some systems for the timescale of the mechanical and chemical signal transmission (14), this timescale was estimated at a singlecell level and not in a multicellular integrated tissue, which is what our work presents as shown in literature on the timescale for mechanical stimulus transmission of the cycle length of actomyosin fluctuation ranges from 1 to 5 min in the Drosophila (20,21), and Xenopus gastrula tissues (22), as well as other induced contractions in Xenopus (16). Additionally, we find the signal transmission distance--the distance between the edge of the ATP stream and the intersection of the negative and positive strains on the strain maps--of the contractile response always extends beyond the regions exposed directly to the ATP stream.…”

Section: Significancesupporting

confidence: 61%

“…1 A and B). ATP can trigger contraction in the Xenopus embryonic epithelium to the same degree as cell lysate (16). Extracellular ATP has been shown to activate contraction in a range of cell types from endothelial cells of the cardiovascular system to skeletal muscle cells (17).…”

Section: Resultsmentioning

confidence: 99%

Mechanochemical actuators of embryonic epithelial contractility

Kim

Hazar

Vijayraghavan

et al. 2014

Self Cite

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 stimulationresponse 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.microfluidics | multicellular | mechanotransduction | signaling P hysiological control systems have evolved diverse strategies to sense the environment, transduce signals, and actuate contractile responses. One such strategy involves the actuation of nonmuscle cell contractility to drive a wide range of developmental processes as well as normal physiological and pathological disease states (1-5). The contractile behaviors of cells and their interactions in multicellular arrays are not only critical in shaping and guiding tissue formation (e.g., epithelial folding) for the successful outcome of development programs (6, 7), but also play a major role in the pathology of tumor growth, the invasionmetastasis cascade, wound healing, and tissue regeneration (8,9).From a signaling standpoint, embryonic development is a dynamic process where cells interact and coordinate force generation as their identities are patterned by spatiotemporally applied chemical stimuli. There has been considerable debate over the effectiveness of intra-versus intercellular signaling during development (10, 11); nevertheless, the cell-cell signaling and the coordination of a variety of multicellular responses are known to be mediated by gap-junction-dependent intercellular communication (12, 13). However, recent findings from studies of cell mechanics indicate that mechanical cues can be as potent as chemical factors in directing cell differentiation and behaviors and suggest a role in modulating signal transduction pathways (14, 15). Less clear is whether signal transduction can be modulated by mechanical connections during morphogenesis. Results and DiscussionTo investigate the complex integrated response of a multicellular system and investigate the mechanochemical response and actuation, we cultured an intact epithelial sheet adhered to a fibronectin extracellular matrix substrate within a custom microfluidic chamber and exposed a narrow band of 4-5 cells...