Modeling Dynamics of Cell-to-Cell Variability in TRAIL-Induced Apoptosis Explains Fractional Killing and Predicts Reversible Resistance
(A) Schematic description of the reactions constituting the stochastic protein turnover model. Gene activity switches, mRNA production and degradation (red arrows) are stochastic reactions. Protein synthesis and degradation reactions (black arrows) are deterministic. (B) For typical mRNA and protein half-lives, promoter switching rates have a limited influence on the protein level half-autocorrelation time: using an analytical derivation of the protein level autocorrelation function (see Supplementary Results, Text S1), the protein half-autocorrelation time is plotted against mean promoter switching times. (C) Behavior of a standard stochastic protein turnover model. Promoter switching rates respect typical ranges observed by Suter et al.  and lead to a protein level coefficient of variation (CV) of 0.25. See Fig. S3 for more details. Upper plots show three representative single-cell time courses of protein and mRNA levels. Histogram at the bottom displays the corresponding distribution of protein level obtained when simulating a large number of cells for a long duration, corresponding to a snapshot of the cell-to-cell variability expected in a population.