Synchrony and Oscillatory Dynamics for a 2-D PDE-ODE Model of Diffusion-Sensing with Small Signaling Compartments

We analyze a class of cell-bulk coupled PDE-ODE models, motivated by quorum and diffusion sensing phenomena in microbial systems, that characterize communication between localized spatially segregated dynamically active signaling compartments or “cells” that have a permeable boundary. In this model, the cells are disks of a common radius and they are spatially coupled through a passive extracellular bulk diffusion field with diffusivity in a bounded 2-D domain. Each cell secretes a signaling chemical into the bulk region at a constant rate and receives a feedback of the bulk chemical from the entire collection of cells. This global feedback, which activates signaling pathways within the cells, modifies the intracellular dynamics according to the external environment. The cell secretion and global feedback are regulated by permeability parameters across the cell membrane. For arbitrary reaction-kinetics within each cell, the method of matched asymptotic expansions is used in the limit of small cell radius to construct steady-state solutions of the PDE-ODE model, and to derive a globally coupled nonlinear matrix eigenvalue problem (GCEP) that characterizes the linear stability properties of the steady-states. The analysis and computation of the nullspace of the GCEP as parameters are varied is central to the linear stability analysis. In the limit of large bulk diffusivity, an asymptotic analysis of the PDE-ODE model leads to a limiting ODE system for the spatial average of the concentration in the bulk region that is coupled to the intracellular dynamics within the cells. Results from the linear stability theory and ODE dynamics are llustrated for Sel’kov reaction-kinetics, where the kinetic parameters are chosen so that each cell is quiescent when uncoupled from the bulk medium. For various specific spatial configurations of cells, the linear stability theory is used to construct phase diagrams in parameter space characterizing where a switch-like emergence of intracellular oscillations can occur through a Hopf bifurcation. The effect of the membrane permeability parameters, the reaction-kinetic parameters, the bulk diffusivity, and the spatial configuration of cells on both the emergence and synchronization of the oscillatory intracellular dynamics, as mediated by the bulk diffusion field, is analyzed in detail. The linear stability theory is validated from full numerical simulations of the PDE-ODE system, and from the reduced ODE model when is large.

Joint work with Sarafa Iyaniwura (UBC) and Jia Gou (UC Riverside).

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