Figure 4

Effect of receptor clustering and density on efficiency of adaptor containment near the membrane. (A) Illustration of particles diffusing in and out of preferred domains or islands. Colored traces show 10 second trajectories of 3 diffusing EGFR particles. Receptors have greater probability to enter preferred domains, where they diffuse 3x slower. When outside of domains, particle diffusion is unconstrained. (B) Particles are clustered at every time step when diffusion is governed in silico by the domain approach. Inset shows results of Hopkins test, confirming clustering is significant. Plots in (C) show that receptor clustering increases the efficiency of Grb2 retainment to EGFR at normal levels of expression (50,000/cell). The frequency of Grb2 docking to another receptor after dissociating from a previous binding event is low when receptors are in the randomly distributed (black line). Increasing receptor cluster size increases the efficiency of adaptor containment near the membrane (grey solid line, 6.57 receptors/cluster; grey dashed line, 100 receptors/cluster). In contrast, if EGFR is overexpressed the plots (D) show no difference in Grb2 rebinding.