Titre :

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

Auteur(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]

Titre de la revue :

Scientific Reports

Éditeur :

Nature Publishing Group

Date de publication :

2020-10-15

ISSN :

2045-2322

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Projet ANR :

Centre Européen pour les Mathématiques, la Physique et leurs Interactions

Collections :

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

Source :

Harvested from HAL