An Asymptotic Analysis of a 2-D Model of Dynamically Active Compartments Coupled by Bulk Diffusion

Abstract: A class of coupled cell-bulk ODE-PDE models is formulated and analyzed in a two-dimensional domain, which is relevant to studying quorum sensing behavior on thin substrates. In this model, spatially segregated dynamically active signaling cells of a common small radius $\epsilon\ll 1$ are coupled through a passive bulk diffusion field. The method of matched asymptotic expansions is used to construct steady-state solutions and to formulate a spectral problem that characterizes the linear stability properties of these solutions, with the aim of predicting whether temporal oscillations can be triggered by the cell-bulk coupling. Phase diagrams in parameter space where such collective oscillations can occur are illustrated for two specific choices of the intracellular kinetics. In the limit of very large bulk diffusion, it is shown that the ODE-PDE system can be approximated by a finite-dimensional dynamical system, which is studied both analytically and numerically. For one illustrative example of the theory it is shown that when the number of cells exceeds some critical number, the bulk diffusion field can trigger oscillations that would otherwise not occur without the coupling. Moreover, for two specific models for the intracellular dynamics, we show that there are rather wide regions in parameter space where these triggered oscillations are synchronous in nature. Unless the bulk diffusivity is asymptotically large, it is shown that a clustered spatial configuration of cells inside the domain leads to larger regions in parameter space where synchronous collective oscillations between the small cells can occur. Finally, the linear stability analysis for these cell-bulk models is shown to be qualitatively rather similar to that of localized spot patterns for activator-inhibitor reaction-diffusion systems in the limit of long-range inhibition and short-range activation.