Distinguishing modes of eukaryotic gradient sensing.

We develop a mathematical model of phosphoinositide-mediated gradient sensing that can be applied to chemotactic behavior in highly motile eukaryotic cells such as Dictyostelium and neutrophils. We generate four variants of our model by adjusting parameters that control the strengths of coupled positive feedbacks and the importance of molecules that translocate from the cytosol to the membrane. Each variant exhibits a qualitatively different mode of gradient sensing. Simulations of characteristic behaviors suggest that differences between the variants are most evident at transitions between efficient gradient detection and failure. Based on these results, we propose criteria to distinguish between possible modes of gradient sensing in real cells, where many biochemical parameters may be unknown. We also identify constraints on parameters required for efficient gradient detection. Finally, our analysis suggests how a cell might transition between responsiveness and nonresponsiveness, and between different modes of gradient sensing, by adjusting its biochemical parameters.