Figure 8: Single-cell temporal EGFR surface expression and ERK activity profiles obtained from stochastic simulations with fluctuating EGFR levels.
From: Relaxation oscillations and hierarchy of feedbacks in MAPK signaling

We considered the effect of extrinsic noise on oscillations in ERK activity. As illustrated in panel (A), which shows representative single-cell simulations, we took EGFR surface expression dynamics to be stochastic and marked by bursts of synthesis/expression of variable size (total amount of EGFR added to the plasma membrane) and duration, with bursts being separated by intervals of variable duration. The bottom four panels show heat maps that indicate single-cell responses (ERK activity as a function of time) to different levels of EGF stimulation: (B) 2 pg/ml, (C) 10 pg/ml, (D) 50 pg/ml, and 200 pg/ml (E). Each row in a heat map corresponds to an individual cell characterized by a unique set of parameters for EGFR surface expression dynamics. The cells considered are otherwise identical. To demonstrate and isolate the effect of EGF dose, we have taken the temporal EGFR expression profile to be the same across panels for each cell (i.e., each row in each heat map corresponds to a common profile). Supplementary Table S3 provides information about the parameters that are unique for the stochastic simulations shown here.