Theoretical study of the impact of adaptation on cell-fate heterogeneity and fractional killing

Theoretical study of the impact of adaptation on cell-fate heterogeneity and fractional killing

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luau thank you cards Abstract Fractional killing illustrates the cell propensity to display a heterogeneous fate response over a wide range of stimuli.The interplay between the nonlinear and stochastic dynamics of biochemical networks plays a fundamental role in shaping this probabilistic response and in reconciling requirements for heterogeneity and controllability of cell-fate decisions.The stress-induced fate choice between life and death depends on an early adaptation response which may contribute to fractional killing by amplifying small differences between cells.To test this hypothesis, we consider a stochastic modeling framework suited for comprehensive sensitivity analysis of dose response curve through the computation of a soderhamn ottoman cover fractionality index.Combining bifurcation analysis and Langevin simulation, we show that adaptation dynamics enhances noise-induced cell-fate heterogeneity by shifting from a saddle-node to a saddle-collision transition scenario.

The generality of this result is further assessed by a computational analysis of a detailed regulatory network model of apoptosis initiation and by a theoretical analysis of stochastic bifurcation mechanisms.Overall, the present study identifies a cooperative interplay between stochastic, adaptation and decision intracellular processes that could promote cell-fate heterogeneity in many contexts.