Mathematical modelling of calcium signalling taking into account mechanical effects

Most of the calcium in the body is stored in bone. The rest is stored elsewhere, and calcium signalling is one of the most important mechanisms of information propagation in the body. Yet, many questions remain open. In this work, we initially consider the mathematical model proposed in Atri et al. [1]. Omitting diffusion, the model is a system of two nonlinear ordinary differential equations (ODEs) for the calcium concentration, and the fraction of IP3 receptors that have not been inactivated by the calcium. We analyse in detail the system as the IP3 concentration, the bifurcation parameter, increases presenting some new insights. We analyse asymptotically the relaxation oscillations of the model by exploiting a separation of timescales. Furthermore, motivated by experimental evidence that cells release calcium when mechanically stimulated and that, in turn, calcium release affects the mechanical behaviour of cells, we propose an extension of the Atri model to a 3D nonlinear ODE mechanochemical model, where the additional equation, derived consistently from a full viscoelastic ansatz, models the evolution of cell/tissue dilatation. Furthermore, in the calcium dynamics equation we introduce a new “stretch-activation” source term that induces calcium release and which involves a new bifurcation parameter, the “strength” of the source. Varying the two bifurcation parameters, we analyse in detail the interplay of the mechanical and the chemical effects, and we find that as the strength of K.Kaouri Department of Electrical Engineering, Computer Engineering, and Informatics Cyprus University of Technology, Cyprus E-mail: [email protected] S. J. Chapman Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford, UK P. K. Maini Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, UK