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

Figure 5

Model fitting to cell fate variability data predicts large, rare fluctuations of Flip/Mcl1 and transient cell fate inheritance.

(A–C) Agreement between model prediction and experimental data for (A) death (i.e. MOMP) time distribution, (B) surviving fraction after 8 hours, and (C) both together, for treatment by TRAIL alone (250 ng/mL), as a function of Flip/Mcl1 promoter switching times (other parameters as in Table S1). (D) Representative protein level fluctuations of Mcl1 described by a stochastic protein turnover model allowing good agreement for both MOMP time distribution and surviving fraction. This model has been used for Figs. 3,4,6 and 7. (E) Model-data agreement for MOMP time correlation between sister cells. For (A), (B), (C) and (E), agreement quality increases from red to green. The quantification algorithm is detailed in Supplementary Methods (Text S1).

Figure 5