Abstract
We develop a coarse-grained stochastic model for the influence of signal relay on the collective behavior of migrating Dictyostelium discoideum cells. In the experiment, cells display a range of collective migration patterns, including uncorrelated motion, formation of partially localized streams, and clumping, depending on the type of cell and the strength of the external, linear concentration gradient of the signaling molecule cyclic adenosine monophosphate (cAMP). From our model, we find that the pattern of migration can be quantitatively described by the competition of two processes, the secretion rate of cAMP by the cells and the degradation rate of cAMP in the gradient chamber. Model simulations are compared to experiments for a wide range of strengths of an external linear-gradient signal. With degradation, the model secreting cells form streams and efficiently transverse the gradient, but without degradation, we find that model secreting cells form clumps without streaming. This indicates that the observed effective collective migration in streams requires not only signal relay but also degradation of the signal. In addition, our model allows us to detect and quantify precursors of correlated motion, even when cells do not exhibit obvious streaming.
Highlights
Eukaryotic cells frequently transduce external chemical gradients into directed cell migration [1], a phenomenon known as chemotaxis
Despite the vast similarities in gradient detection among D. discoideum and mammalian cells including neutrophils and neurons, D. discoideum chemotaxis displays a striking collective phenomenon not often found in other cell types where D. discoideum cells responding to the extracellular chemical signal cyclic-AMP tend to migrate in a head-totail fashion termed streams
If not modulated by cAMP or by PDE1 secreted by the cells, the imposed gradient stays constant at least for 60 minutes [47,51]
Summary
Eukaryotic cells frequently transduce external chemical gradients into directed cell migration [1], a phenomenon known as chemotaxis. Seminal work in the last few decades has identified components of the intracellular biochemical networks mediating cell response to external chemical gradients and found that responsive components such as the phosphoinositide lipids (PIPs), PI3K, and PTEN are highly conserved across cell types. In these efforts, our model organism (Dictyostelium discoideum) has been a useful source for discovery of network components and the development of quantitative models exploring plausible mechanisms for mediating directional sensing. Many cell types, including neutrophils, macrophages, and epithelial cells, have potential signal relay loops, but they do not tend to migrate in streams in a standard chemotaxis assay
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