Simulations of epidermal growth factor receptor dynamics on corralled membrane surfaces

The current understanding of how receptors diffuse and cluster in the plasma membrane of living cells is limited. Single particle tracking and laser tweezer experiments have suggested that membrane diffusion is affected by cytoskeleton-associated barriers dividing the membrane into corrals. Herein, we have developed models to simulate the effect of corrals on the diffusion and dimerization/clustering of receptors in the plasma membrane, focusing mainly on the epidermal growth factor receptor.; First, a Monte Carlo model for receptor diffusion on a corralled surface was developed. The results of this simulation confirm that a fence barrier (the ratio of the transition probability for diffusion across a fence to that within a corral) on the order of 103--104 recreates the experimentally measured difference in diffusivity between artificial and natural plasma membranes. We also examine whether a lattice model is an appropriate description of the plasma membrane and study three different sets of boundary conditions that describe diffusion over barriers. This analysis reveals that diffusion events on the plasma membrane may occur with a physically relevant length scale characteristic of an exchange mechanism with lipids.; Next, dimerization and clustering were studied using two different models: a well-mixed population balance model and a lattice Monte Carlo model. The average cluster size results for time scales between 1 ms and 10 seconds were found to be very similar. This is because the reaction rate parameters used herein from the literature correspond to a reaction-limited system.; To test whether the combination of dimerization and corralled diffusion can affect the spatial distribution of receptors, the reaction rates were increased within reasonable values, and simulations were run with an uneven initial distribution of receptors. Under these conditions, receptors in the initially dense region dimerized and remained in their initial corral for at least one tenth of a second simulated. These simulations indicate that localization of receptors in certain regions, such as corrals, due to, for example, interactions with other lipids, coupled with dimerization and fence barriers can provide a mechanism for localization of receptors over longer periods of time.