Cellular diffusion processes in singularly perturbed domains

There are many processes in cell biology that can be modeled in terms of particles diffusing in a two-dimensional (2D) or three-dimensional (3D) bounded domain $\Omega \subset R^d$ containing a set of small subdomains or interior compartments $U_j$ , $j=1,\dots ,N$ (singularly-perturbed diffusion problems). The domain $\Omega$ could represent the cell membrane, the cell cytoplasm, the cell nucleus or the extracellular volume, while an individual compartment could represent a synapse, a membrane protein cluster, a biological condensate, or a quorum sensing bacterial cell. In this review we use a combination of matched asymptotic analysis and Green's function methods to solve a general type of singular boundary value problems (BVP) in 2D and 3D, in which an inhomogeneous Robin condition is imposed on each interior boundary $\partial U_j$ . This allows us to incorporate a variety of previous studies of singularly perturbed diffusion problems into a single mathematical modeling framework. We mainly focus on steady-state solutions and the approach to steady-state, but also highlight some of the current challenges in dealing with time-dependent solutions and randomly switching processes.