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A simple mechanochemical model for calcium signalling in embryonic epithelial cells

Kaouri, Katerina, Maini, P.K., Christodoulou, N., Skourides, P. and Chapman, S.J. 2019. A simple mechanochemical model for calcium signalling in embryonic epithelial cells. Journal of Mathematical Biology 78 (7) , pp. 2059-2092. 10.1007/s00285-019-01333-8

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Calcium (Ca2+) signalling is one of the most important mechanisms of information propagation in the body. In embryogenesis the interplay between Ca2+ signalling and mechanical forces is critical to the healthy development of an embryo but poorly understood. Several types of embryonic cells exhibit calcium-induced contractions and many experiments indicate that Ca2+ signals and contractions are coupled via a two-way mechanochemical coupling. We present a new analysis of experimental data that supports the existence of this coupling during Apical Constriction in Neural Tube Closure. We then propose a mechanochemical model, building on early models that couple Ca2+ dynamics to cell mechanics and replace the bistable Ca2+ release with modern, experimentally validated Ca2+ dynamics. We assume that the cell is a linear viscoelastic material and model the Ca2+-induced contraction stress with a Hill function saturating at high Ca2+ levels. We also express, for the first time, the "stretch-activation" Ca2+ flux in the early mechanochemical models as a bottom-up contribution from stretch-sensitive Ca2+ channels on the cell membrane. We reduce the model to three ordinary differential equations and analyse its bifurcation structure semi-analytically as the IP3 concentration, and the "strength" of stretch activation, λ vary. The Ca2+ system (λ=0, no mechanics) exhibits relaxation oscillations for a certain range of IP3 values. As λ is increased the range of IP3 values decreases, the oscillation amplitude decreases and the frequency increases. Oscillations vanish for a sufficiently high value of λ. These results agree with experiments in embryonic cells that also link the loss of Ca2+ oscillations to embryo abnormalities. The work addresses a very important and understudied question on the coupling of chemical and mechanical signalling in embryogenesis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Mathematics
Publisher: Springer Verlag
ISSN: 0303-6812
Related URLs:
Date of First Compliant Deposit: 6 February 2019
Date of Acceptance: 5 February 2019
Last Modified: 04 Jun 2019 09:49

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