2 March 2019
Journal of Mathematical Biology
Calcium signalling is one of the most important mechanisms of information propagation in the body. In embryogenesis the interplay between calcium 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 calcium signals and contractions are coupled via a two-way mechanochemical feedback mechanism. We present a new analysis of experimental data that supports the existence of this coupling during Apical Constriction. We then propose a simple mechanochemical model, building on early models that couple calcium dynamics to the cell mechanics and we replace the hypothetical bistable calcium release with modern, experimentally validated calcium dynamics. We assume that the cell is a linear, viscoelastic material and we model the calcium-induced contraction stress with a Hill function, i.e. saturating at high calcium levels. We also express, for the first time, the “stretch-activation” calcium flux in the early mechanochemical models as a bottom-up contribution from stretch-sensitive calcium channels on the cell membrane. We reduce the model to three ordinary differential equations and analyse its bifurcation structure semi-analytically as two bifurcation parameters vary - the IP3 concentration, and the “strength” of stretch activation, λ. The calcium 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 and oscillations eventually vanish at a sufficiently high value of λ. This result agrees with experimental evidence in embryonic cells which also links the loss of calcium oscillations to embryo abnormalities. Furthermore, as λ is increased the oscillation amplitude decreases but the frequency increases. Finally, we also identify the parameter range for oscillations as the mechanical responsiveness factor of the cytosol increases. This work addresses a very important and understudied question regarding the coupling between chemical and mechanical signalling in embryogenesis.
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