Grid-free stochastic simulations of reaction-diffusion processes at cell-cell contacts

Abstract: Biological cells can exchange messages through soluble molecules or membrane-bound receptors. In particular in the latter case, the interaction is usually located in specific regions of the interacting cells and may depend on or induce local morphological features or reorganizations of the membrane-associated or membrane-proximal biochemistry. Examples are interactions among cells that probe their environment and the surfaces of neighboring cells with dendrite-like protrusions. Previously, we introduced an algorithm capable of creating spatially-resolved, stochastic particle-based computational models of cellular biochemistry. However, its applicability was limited to the case of soluble ligands. Here, building on this earlier approach, we introduce a simulation method that accounts for the unique features that distinguish the sites of cell-cell contact from other regions of the cell membrane. Employing a smooth, grid-free computational representation of the contact sites, we extend the applicability of Green's function-based stochastic simulation algorithms to study intermembrane bimolecular interactions between particles on adjacent curved surfaces. We demonstrate the utility of this computational approach by exploring the effects of contact geometry and local biochemistry for the early phase of T-cell receptor activation.