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Modeling Dynamics of Cell-to-Cell Variability in TRAIL-Induced Apoptosis Explains Fractional Killing and Predicts Reversible Resistance

Figure 3

Cell fate variability in TRAIL-induced apoptosis.

(A–C) Cell fate variability experiments performed in [13]. (A) HeLa cell populations were treated with either 10 ng/mL of TRAIL and 2.5 µg/mL of cycloheximide (CHX) or 250 ng/mL of TRAIL alone. Cells were tracked during 8 hours by live-cell microscopy and MOMP time was detected via mitochondrial release of a fluorescent reporter. (B–C) Histograms of MOMP times and surviving fractions observed for treatment with (B) TRAIL and CHX or (C) TRAIL alone. (D–F) In-silico reproduction of those experiments with our “fitted” model (i.e. the parameterization in the explored parameter space region giving the best agreement for cell fate variability data, described in Tables S1-3). (D) Simulations (see Supplementary Methods in Text S1 for details). (E–F) Results for the (E) TRAIL and CHX or (F) TRAIL alone treatments. For the latter case, representative model trajectories are given in Fig. S9.

Figure 3