A Conceptual Molecular Network for Chemotactic Behaviors Characterized by Feedback of Molecules Cycling Between the Membrane and the Cytosol

Cell chemotaxis has been characterized as the formation of a front-back axis that is triggered by a gradient of chemoattractant; however, chemotaxis is accompanied by more complicated behaviors. These include migration in a straight line with a stable axis [the stable single-axis (SSA) pattern] and repeated splitting of the leading edge of the cell into two regions, followed by the choice of one of these as the new leading edge [the split and choice (S&C) pattern]. Indeed, transition between these two behaviors can be observed in individual cells. However, the conceptual framework of the network of signaling molecules that generates these patterns remains to be clarified. We confirmed theoretically that a system that has positive and negative feedback loops involving the reciprocal cycling between the membrane and the cytosol of molecules that promote membrane protrusion or retraction generates SSA and S&C patterns of migratory behavior under similar conditions. We also predicted properties of the instabilities of such a system, which are essential for the generation of these behaviors, and we verified their existence in chemotaxing cells. Our research provides a simple model of network structure for chemotactic behaviors, including cell polarization.