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

Figure 7

Molecular determinants of cell fate and resistance to repeated TRAIL treatments.

(A) Cartoon illustrating that the determinants of cell fate and resistance can be studied by analyzing the over-representation of protein levels in ‘future survivors’ (cells that will still be alive after treatment) at the time of treatment, and in surviving cells at day X, respectively. (B) Cell fate determinants analysis: over-representation (compared to initial population) of protein level (blue) and promoter activity (red) at the time of treatment in ‘future survivors’. Asterisks mark differences that passed a 5% significance test. (C) Resistance determinants analysis: over-representation of protein levels in surviving cells at day X. Inset illustrates the recovery kinetics expected from protein turnover only (i.e. in absence of significant selection effect or residual signaling activity). Therefore, deviation from such kinetics indicates the presence of a selection effect or residual signaling activity.

Figure 7

doi: https://doi.org/10.1371/journal.pcbi.1003893.g007