Intrinsic noise, dissipation cost, and robustness of cellular networks: the underlying energy landscape of MAPK signal transduction.

Proceedings of the National Academy of Sciences of the United States of America
Saul LapidusJin Wang

Abstract

We develop a probabilistic method for analyzing global features of a cellular network under intrinsic statistical fluctuations, which is important when there are finite numbers of molecules. By making a self-consistent mean field approximation of splitting the variables in order to reduce the large number of degrees of freedom, which is reasonable for a not very strongly interacting network, we discovered that the underlying energy landscape of the mitogen-activated protein kinases (MAPKs) signal transduction network (with experimentally measured or inferred parameters such as chemical reaction rate coefficients in the network) is funneled toward a global minimum characterized by the nonequilibrium steady-state fixed point of the system at the end of the signal transduction process. For this system, we also show that the energy landscape is robust against intrinsic fluctuations and random perturbation to the inherent chemical reaction rates. The ratio of the slope versus the roughness of the energy landscape becomes a quantitative measure of robustness and stability of the network. Furthermore, we quantify the dissipation cost of this nonequilibrium system through entropy production, caused by the nonequilibrium flux in the sys...Continue Reading

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Citations

Aug 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jin WangErkang Wang
Jul 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Xiao-Peng ZhangWei Wang
Apr 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jin WangErkang Wang
Oct 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Youfang CaoJie Liang
Apr 1, 2011·BMC Genomics·Peter T VedellGary A Churchill
May 31, 2011·BMC Systems Biology·Sudin BhattacharyaMelvin E Andersen
Jan 15, 2014·PLoS Computational Biology·Garrett Jenkinson, John Goutsias
Feb 6, 2014·PloS One·Li XuJin Wang
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Han YanJin Wang
Aug 18, 2012·The Journal of Chemical Physics·Feng ZhangJin Wang
Apr 8, 2010·The Journal of Chemical Physics·Ge Wang, Muhammad H Zaman
Jun 25, 2009·The Journal of Chemical Physics·Mark KnessMuhammad H Zaman
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Aug 14, 2008·Physical Biology·Ting LuJeff Hasty
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May 7, 2013·The Journal of Physical Chemistry. B·Chen Liao, Ting Lu
Dec 30, 2010·The Journal of Physical Chemistry. B·Haidong FengJin Wang
Oct 10, 2021·Cell Systems·Megan A CoomerMichael P H Stumpf

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