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

Blog Article

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 Security System 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 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 B12 METHYL present study identifies a cooperative interplay between stochastic, adaptation and decision intracellular processes that could promote cell-fate heterogeneity in many contexts.