Title :

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

Author(s) :

Hurbain, Julien [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Labavić, Darka [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Thommen, Quentin [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Pfeuty, Benjamin [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]

Journal title :

SCIENTIFIC REPORTS

Publisher :

Nature Publishing Group

Publication date :

2020-10-15

ISSN :

2045-2322

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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 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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Laboratoire de Physique des Lasers, Atomes et Molécules (PhLAM) - UMR 8523

Source :

Harvested from HAL