Model of the initiation of signal transduction by ligands in a cell culture: Simulation of molecules near a plane membrane comprising receptors

Cell communication is a key mechanism in tissue responses to radiation. Several molecules are implicated in radiation-induced signaling between cells, but their contributions to radiation risk are poorly understood. Meanwhile, Green's functions for diffusion-influenced reactions have appeared in the literature, which are applied to describe the diffusion of molecules near a plane membrane comprising bound receptors with the possibility of reversible binding of a ligand and activation of signal transduction proteins by the ligand-receptor complex. We have developed Brownian dynamics algorithms to simulate particle histories in this system which can accurately reproduce the theoretical distribution of distances of a ligand from the membrane, the number of reversibly bound particles, and the number of receptor complexes activating signaling proteins as a function of time, regardless of the number of time steps used for the simulation. These simulations will be of great importance to model interactions at low doses where stochastic effects induced by a small number of molecules or interactions come into play.