Stochastic modelling for gradient sensing by chemotactic cells

Abstract

Chemotaxis, the process by which cells move toward attractant molecules, operates in a range of biological processes including immunity, neuronal patterning, and morphogenesis. Dictyostelium discoideum cells display a strong chemotactic response to cyclic adenosine 3′,5′-monophosphate (cAMP), which binds to a cell surface receptor. Each Dictyostelium has ca. 80000 cAMP receptors, and can transduce shallow spatial chemoattractant gradients into strongly localized intracellular responses in spite of large statistical fluctuation of receptor occupancy even in the case of very low cAMP concentration. In this study, we develop a stochastic model for gradient sensing by chemotactic cells. We simulate the binding of cAMP molecules to receptors by a Monte-Carlo method in order to account for statistical fluctuation of receptor occupancy and treat intracellular signal processing by a diffusion-translocation model, which includes the production of second-messenger molecules and positive feedback mechanisms mediated by effector molecules. Our simulation results show that the fluctuation of second-messenger concentration is much smaller than that of receptor occupancy, and that a shallow chemoattractant gradient are transduced into a large second-messenger concentration gradient through nonlinear signal amplification. © 2004 Elsevier Ltd. All rights reserved.