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

Figure 1

Accounting for stochastic protein turnover in signal transduction pathways.

Scheme of the modeling approach. Protein-protein interactions mediating signal transduction (signal transduction layer) are modeled by ordinary differential equations. In parallel, promoter activity changes, mRNA production and degradation (gene expression layer) are seen as stochastic events and generate fluctuations in mRNA levels. This impacts the synthesis rates of the corresponding proteins. Together with protein degradation, it generates fluctuations in protein levels (here shown in absence of transduction). Only a fragment of the extrinsic apoptosis pathway is shown. Deterministic/stochastic interpretation of chemical reactions is represented with black/red arrows respectively.

Figure 1