Excitable Signal Relay and Emergent Behavior in Dictyostelium Discoideum

Abstract

The social amoeba <italic>Dictyostelium discoideum</italic> displays elobrate emergent behaviors upon starvation. Hundreds of cells communicate via the signaling molecule cyclic adenosine 3',5'-monophosphate (cAMP) and then aggregate into multicellular spore bodies. In this process, cells periodically emit cAMP and thereby create radial gradients along which surrounding cells travel back toward the transmitting cells. The cAMP also causes the surrounding cells to emit cAMP of their own thus propagating the signal throughout the population. The cells simultaneously display many interesting collective phenomena like pattern formation, collective oscillations and cell differentiation. Though many aspects of these phenomena have been extensively studied, the effects of the underlying molecular mechanisms on emergent collective behavior are not well understood. This work provides a preliminary account of these origins in <italic>Dictyostelium discoideum</italic>.

In this thesis, we have employed a compound fluorescent protein whose emission spectrum changes with the surrounding concentration of cAMP. This sensor allows us to monitor, in real time and in vivo, concentrations of cAMP within individual cells. Cells expressing this protein are loaded into custom microfabricated environments and subjected to dynamic external cAMP stimulation which in turn induces transient and periodic changes in internal cAMP. By monitoring the response of the intracellular cAMP to various external concentration profiles, we show that the cAMP transduction pathway in <italic>Dictyostelium</italic> cells is well described by the FitzHugh-Nagumo model, an excitable dynamical system much like that found in neuronal action potentials. The model accounts for the excitable and oscillatory behavior of single cells and sets groundwork for a more comprehensive multicellular model that promises to explain periodic cAMP signaling in populations.