article · 01/01/2019
Scaling laws of cell-fate responses to transient stress
Résumé
Analysis and modelling of dose-survival curves of cells and tissues are often used to assess therapeutic efficacy or environmental risks, much less to infer the intracellular regulatory mechanisms of cellular stress response. However, systematic measurements of how cell survival depends on the time profile of stress, such as exposure duration, provide practical means to decipher the homeostatic dynamics of stress-response regulatory networks. In this paper, we propose a dynamical framework to theoretically address the relationship between cell fate response to a transient stress and the underlying regulatory feedback mechanisms. A simple network topology that couples a homeostatic negative feedback and a death-triggering positive feedback is shown to display four response regimes for which the iso-effect relationships between duration and intensity are captured by specific power laws. These distinct response regimes define several windows of stress duration for which lethality is not merely proportional to the product of intensity and duration, and, thus, for which cells are either more tolerant or more vulnerable to a given dose. Overall, this study highlights the differential roles of feedback strength, timescale and nonlinearity in promoting survivability to particular stress profiles, providing a valuable framework for a comparative analysis of diverse stress-specific regulatory networks. (C) 2019 Elsevier Ltd. All rights reserved.
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Labavic, D., Ladjimi, M.-T., Thommen, Q., & Pfeuty, B. (2019). Scaling laws of cell-fate responses to transient stress. J. Theor. Biol., 478(IN5JS). https://doi.org/10.1016/j.jtbi.2019.06.014@article{Labavic2019_353,
author = {Labavic, Darka and Ladjimi, Mohamed Tahar and Thommen, Quentin and Pfeuty, Benjamin},
year = {2019},
month = {1},
title = {Scaling laws of cell-fate responses to transient stress},
journal = {J. Theor. Biol.},
publisher = {ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD},
volume = {478},
number = {IN5JS},
address = {24-28 OVAL RD, LONDON NW1 7DX, ENGLAND},
abstract = {Analysis and modelling of dose-survival curves of cells and tissues are often used to assess therapeutic efficacy or environmental risks, much less to infer the intracellular regulatory mechanisms of cellular stress response. However, systematic measurements of how cell survival depends on the time profile of stress, such as exposure duration, provide practical means to decipher the homeostatic dynamics of stress-response regulatory networks. In this paper, we propose a dynamical framework to theoretically address the relationship between cell fate response to a transient stress and the underlying regulatory feedback mechanisms. A simple network topology that couples a homeostatic negative feedback and a death-triggering positive feedback is shown to display four response regimes for which the iso-effect relationships between duration and intensity are captured by specific power laws. These distinct response regimes define several windows of stress duration for which lethality is not merely proportional to the product of intensity and duration, and, thus, for which cells are either more tolerant or more vulnerable to a given dose. Overall, this study highlights the differential roles of feedback strength, timescale and nonlinearity in promoting survivability to particular stress profiles, providing a valuable framework for a comparative analysis of diverse stress-specific regulatory networks. (C) 2019 Elsevier Ltd. All rights reserved.},
url = {http://www.dx.doi.org/10.1016/j.jtbi.2019.06.014},
doi = {10.1016/j.jtbi.2019.06.014},
issn = {0022-5193},
}TY - JOUR
AU - Labavic, Darka
AU - Ladjimi, Mohamed Tahar
AU - Thommen, Quentin
AU - Pfeuty, Benjamin
PY - 2019
DA - 2019/01/01
TI - Scaling laws of cell-fate responses to transient stress
JO - J. Theor. Biol.
VL - 478
IS - IN5JS
PB - ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
SN - 0022-5193
AB - Analysis and modelling of dose-survival curves of cells and tissues are often used to assess therapeutic efficacy or environmental risks, much less to infer the intracellular regulatory mechanisms of cellular stress response. However, systematic measurements of how cell survival depends on the time profile of stress, such as exposure duration, provide practical means to decipher the homeostatic dynamics of stress-response regulatory networks. In this paper, we propose a dynamical framework to theoretically address the relationship between cell fate response to a transient stress and the underlying regulatory feedback mechanisms. A simple network topology that couples a homeostatic negative feedback and a death-triggering positive feedback is shown to display four response regimes for which the iso-effect relationships between duration and intensity are captured by specific power laws. These distinct response regimes define several windows of stress duration for which lethality is not merely proportional to the product of intensity and duration, and, thus, for which cells are either more tolerant or more vulnerable to a given dose. Overall, this study highlights the differential roles of feedback strength, timescale and nonlinearity in promoting survivability to particular stress profiles, providing a valuable framework for a comparative analysis of diverse stress-specific regulatory networks. (C) 2019 Elsevier Ltd. All rights reserved.
DO - 10.1016/j.jtbi.2019.06.014
UR - http://www.dx.doi.org/10.1016/j.jtbi.2019.06.014
ER -