Compartmentalization of Receptors and Enzymes Affects Activation for a Collision Coupling Mechanism

Enzyme (e.g. G-protein) activation occurring via collisions between receptor-ligand complexes and enzymes in the plasma membrane is thought to be an early event in signal transduction leading to a cellular response. Evidence is accumulating that suggests the species involved may not be distributed homogeneously throughout the plasma membrane. Rather, they may be organized into reaction compartments or domains. We investigate the expected effects of these domains on reaction kinetics and enzyme activation for activation by a collision coupling mechanism. Monte Carlo techniques are used to simulate the reaction and diffusion of molecules in the plasma membrane. The reaction kinetics and levels of activated enzymes at steady state are characterized in terms of the physical properties of the tissue (e.g. receptor density, domain diameter) and ligand (e.g. binding kinetics). The reaction rate constant does not simply scale with the fractional coverage of the domains. Two additional properties which affect the reaction rate constant are (1) the mean square displacement of a receptor-ligand complex relative to the size of the domain and (2) the distribution of receptors and enzymes into the domains.