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Abstract

Boundary-driven oscillations were numerically predicted to exist in a reaction–diffusion–advection system, namely in the signaling population of social amoeba D. discoideum. If deprived of nutrients, D. discoideum aggregates by producing cAMP waves at precisely timed intervals. In the presence of an advecting flow, holding the upstream boundary to a zero concentration of cAMP produces an instability that sends periodic wave trains downstream. This instability is expected to exist at lower degradation rates of cAMP and thus provides a mechanism for wave creation in phosphodiesterase deficient systems, such as PdsA− cells. Degradation of extracellular cAMP by the enzyme phosphodiesterase PdsA is fundamental to successfully producing waves, regulating the external cAMP gradient field and preventing the accumulation of cAMP. Using a flow-through microfluidic setup filled with PdsA− cells, we confirm experimentally that boundary-driven oscillations indeed exist. Above a minimum flow velocity, decaying waves are induced, with a decay length that increases with the imposed flow velocity. We performed extensive numerical simulations and showed that these waves have a boundary-driven origin, where the lack of cAMP in the upstream flow destabilizes the system. We explored the properties of these waves and the parameter region where they exist, finding good agreement with our experimental observations. These results provide experimental confirmation of the destabilizing effect of the upstream boundary in an otherwise stable reaction-diffusion system. We expect this mechanism to be relevant for wave creation in other oscillatory or excitable systems that are incapable of wave generation in the absence of flow.