Local accumulation time for diffusion in cells with gap junction coupling

TL;DR

This paper investigates how cells with gap junctions reach steady-state diffusion, focusing on local accumulation time to understand spatial relaxation dynamics in static and stochastic junction models, including linear cell arrays.

Contribution

It introduces the analysis of local accumulation time for diffusion in coupled cells, considering both static and dynamic gap junction models, extending to linear cell arrays.

Findings

Accumulation time increases monotonically with distance from the source.

Discontinuity in accumulation time at the gap junction diminishes as permeability increases.

Results generalize to linear arrays of cells with gap junction coupling.

Abstract

In this paper we analyze the relaxation to steady-state of intracellular diffusion in a pair of cells with gap-junction coupling. Gap junctions are prevalent in most animal organs and tissues, providing a direct diffusion pathway for both electrical and chemical communication between cells. Most analytical models of gap junctions focus on the steady-state diffusive flux and the associated effective diffusivity. Here we investigate the relaxation to steady state in terms of the so-called local accumulation time. The latter is commonly used to estimate the time to form a protein concentration gradient during morphogenesis. The basic idea is to treat the fractional deviation from the steady-state concentration as a cumulative distribution for the local accumulation time. One of the useful features of the local accumulation time is that it takes into account the fact that different spatial regions can relax at different rates. We consider both static and dynamic gap junction models. The former treats the gap junction as a resistive channel with effective permeability $\mu$, whereas the latter represents the gap junction as a stochastic gate that randomly switches between an open and closed state. The local accumulation time is calculated by solving the diffusion equation in Laplace space and then taking the small-$s$ limit. We show that the accumulation time is a monotonically increasing function of spatial position, with a jump discontinuity at the gap junction. This discontinuity vanishes in the limit $\mu \rightarrow \infty$ for a static junction and $\beta \rightarrow 0$ for a stochastically-gated junction, where $\beta$ is the rate at which the gate closes. Finally, our results are generalized to the case of a linear array of cells with nearest neighbor gap junction coupling.