Figure 2

Bimodal switch of p53 dynamics and its correlation with cell-fate outcome. (a) Cumulative survival curves for U-2 OS cells treated with etoposide at the indicated dose from 1 to 150 μmol/l. The total number of cells analyzed for each curve ranged from 77 to 113, and varied between conditions. Individual cells were monitored by phase-contrast and fluorescence time-lapse microscopy from drug addition for 72 hours or until morphological death occurred. Kinetics of cell death were plotted as cumulative survival curves. (b) Distribution of the four response phenotypes with respect to p53 dynamics and cell fate (as discussed in the text) to DNA damage triggered by etoposide at the indicated doses. Error bars show standard deviations (SDs) of data from two independent experiments. (c) Single-cell trajectories of p53 dynamics at the nucleus quantified from the A549-p53 reporter line. (d) Distribution of the four response phenotypes in A549 cells at the indicated etoposide doses. The total number of cells analyzed for each concentration ranged from 81 to 106. Error bars show SDs of data from two independent experiments. (e) Characteristics of the two p53 dynamic modes in individual cells (denoted by the black dots) and the population average (denoted by the red bars). (Left) pulsing period and pulsing amplitude; (right) rate of monotonic increase and maximum amplitude. Thirty cells were analyzed for each drug concentration. Error bars show SDs of data from the 30 individual cells.