REDUCTION-OF-DIMENSIONALITY KINETICS AT REACTION-LIMITED CELL-SURFACERECEPTORS

It has been suggested for several years that reactions between ligands and cell surface receptors can be speeded up by nonspecific adsorptio n of the ligand to the cell surface followed by two-dimensional surfac e diffusion to the receptor, a mechanism referred to as ''reduction-of -dimensionality'' (RD) rate enhancement. Most of the theoretical treat ments of this and related problems have assumed that the receptor is a n irreversibly absorbing perfect sink. Such receptors induce a depleti on zone of ligand probability density around themselves. The reaction rate in this case (called ''diffusion-limited'') is limited only by th e time required for ligands to diffuse through this depletion zone. In some cases, however, the receptor may be far from ''perfect'' such th at a collision with a ligand only rarely leads to binding. Receptors t hen do not create significant local depletion zones of ligand probabil ity density, and the reaction rate becomes strongly affected by the (s mall) probability of reaction success per diffusive encounter (the ''r eaction-limited'' case). This article presents a simple theory of RD r ate enhancement for reaction-limited receptors that are either reversi ble or irreversible binders. In contrast to the diffusion-limited theo ries, the reaction-limited theory presented here: (a) differs quantita tively from diffusion-limited models; (b) is simple and algebraic in c losed form; (c) exhibits significant rate enhancement in some realisti c cases; (d) depends strongly on the actual Brownian rather than pure diffusive nature of the ligand's motion; (a) depends (for irreversibly binding receptors only) on the kinetic rates (not just equilibria) of reversible adsorption to nontarget regions, in contrast to some previ ous approximate theories of reduction of dimensionality; and (f) is ap plicable to actual ligand/receptor systems with binding success probab ilities at the opposite extreme from the perfect sink/diffusion-limite d models.