Abstract
AbstractA common signature of cell adaptation to stress is the improved resistance upon priming by prior stress exposure. In the context of hyperthermia, priming or preconditioning with sublethal heat shock can be a useful tool to confer thermotolerance and competitive advantage to cells. In the present study, we develop a data-driven modeling framework that is simple and generic enough to capture a broad set of adaptation behaviors to heat stress at both molecular and cellular levels. The model recovers the main features of thermotolerance and clarifies the tradeoff principles which maximize the thermotolerance effect. It therefore provides an effective predictive tool to design preconditioning and fractionation hyperthermia protocols for therapeutic purpose.
Publisher
Cold Spring Harbor Laboratory
Reference45 articles.
1. Dose response relationship in anti-stress gene regulatory networks;PLoS Comput. Biol,2007
2. Evolutionary tradeoffs between economy and effectiveness in biological homeostasis systems;PLoS Comput. Biol,2013
3. Scaling laws of cell-fate responses to transient stress;J. Theor. Biol,2019
4. Cellular stress response pathway system as a sentinel ensemble in toxicological screening;Toxicol. Sci,2009
5. Theoretical study of the impact of adaptation on cell-fate heterogeneity and fractional killing;Scientific Reports,2020