Cellular individuality in gradient sensing of Dictyostelium
It is generally assumed that single cells in an isogenic population, when exposed to an identical environment, exhibit the same behavior. However, it is becoming increasingly clear that even in a genetically identical population gene expression levels can vary significantly from cell-to-cell giving rise to non-genetic individuality. It is an open question whether a conceptually similar individuality can be observed at the signal transduction level. For example, it is unknown how the fidelity of detecting an extracellular cue varies from cell-to-cell.
Here we explore this individuality in the gradient sensing response of single Dictyostelium cells when exposed to repeated spatio-temporal pulses of the chemoattractant cAMP. We find that the response of a single cell is highly reproducible from pulse-to-pulse. In contrast, a large variability in the response direction and response magnitude is observed from cell-to-cell, even when different cells are exposed to the same pulse.
We propose that the effective signal a cell detects is the product of the extracellular cAMP signal and an intracellular signal of which the direction and magnitude vary from cell-to-cell. Using this model we successfully predict the observed variability in directional sensing. This stochastic aspect of directional sensing might, on one hand, fundamentally limit the fidelity of signal detection and, on the other hand, might be beneficial by diversifying phenotypes in an isogenic population.
Figure 1: Dynamic translocation of CRAC-GFP at the plasma membrane after stimulation with a 2 second pulse of cAMP.
Figure 2: Comparison between response of a single cell, which is stimulated 10 times and a population of 40 cells, which is stimulated once.