MEFs responses to TNF-α stimulation.

<p>(<b>A</b>) Graphical representation of a <i>NT</i> time series. A sequence of relative minimum (red ‘x’), maximum (blue ‘x’) and minimum identify a peak. The two quantities θ_L and θ_R are used to determine whether the second peak is significant. Other descriptors of the cell response to the stimulus are reported: timing of the response (T_response), the response value NT(T_response,) and the area under the response peak, defined as the area of the peak confined by its two local minima (shaded in orange). (<b>B</b>)The graph plots the probability of having a short-term fluctuation as a function of their θ value, θ_fluc. Overall, short-term fluctuations have an average value of θ_fluc close to 0.012. From over more than 10⁴ short term fluctuations we find none with θ≥0.06. (<b>C</b>) Significant peaks (maximum and minima denoted by red and blue ‘x’ respectively) have θ≥0.06, other fluctuations are considered noise (black ‘x’). (<b>D</b>) Time series obtained with 10 ng/ml TNF-α and (<b>E</b>) 1 ng/ml TNF-α. Blue symbols represent the maximum of the first significant peak observed for each cell in the first 2 hours and denote a responding cell. The black line denotes the average of the time series, which looks strongly damped due to the asynchrony and heterogeneity of the dynamics at single cell level, plotted in green. (<b>F</b>) Fraction of responding cells as a function of TNF-α concentration. (<b>G</b>) Timing of the maximum of the response peak after stimulation as a function of TNF-α concentration. (<b>H</b>) The maximal value of the response peak increases with TNF-α doses and appears to plateau at 10 ng/ml. (<b>I</b>) The area under the response peak is remarkably constant with increasing TNF-α doses. In panels from (<b>F</b>) to (<b>I</b>), each symbol corresponds to an independent experiment; error bars represent standard deviation.