Stochasticity in membrane-localized "ligand-receptor-G protein" binding: Consequences for leukocyte movement behavior

The signal that governs the chemotactic response of mammalian white blood cells and tissue cells arises from membrane-localized binding events involving chemotactic factor ligands and receptors and G proteins. Fluctuations in this signal have been traditionally attributed to significant "noise" in receptor-ligand binding owing to a limited number of receptors. This paper examines the validity and consequences of a new hypothesis which states that the noise could be associated with a limited number of G proteins as well as receptors. This work characterizes via stochastic analysis and simulation the effects of the relative sizes of G protein and receptor populations on the variance of fluctuations of receptor states and consequently on the directional persistence behavior of cells in uniform chemotactic factor concentrations under the assumptions of the model used to link a G protein-mediated receptor signal to cell turning. Our results suggest that there may exist an optimal number of G proteins through which chemotactic receptors can signal that maximizes cell orientation accuracy in a chemotactic factor gradient.