Sun, 27 Jul 2008 06:13:53 BST CiteULike: cactus's cell http://www.citeulike.org/user/cactus/tag/cell CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/cactus/article/2689148 <i>Proceedings of the National Academy of Sciences (17 April 2008), 0708708105.</i><br /><br />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 system. We found that a lower dissipation cost corresponds to a more robust network. This least dissipation property might provide a design principle for robust and functional networks. Finally, we find the possibility of bistable and oscillatory-like solutions, which are important for cell fate decisions, upon perturbations. The method described here can be used in a variety of biological networks. 10.1073/pnas.0708708105 Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction Saul Lapidus Bo Han Jin Wang doi:10.1073/pnas.0708708105 Proceedings of the National Academy of Sciences (17 April 2008), 0708708105. 2008-04-18T18:35:19-00:00 2008 Proceedings of the National Academy of Sciences 0708708105 cell network signal http://www.citeulike.org/user/cactus/article/2744921 <i>Proceedings of the National Academy of Sciences, Vol. 105, No. 14. (8 April 2008), pp. 5373-5377.</i><br /><br />Swimming Escherichia coli responds to changes in temperature by modifying its motor behavior. Previous studies using populations of cells have shown that E. coli accumulate in spatial thermal gradients, but these experiments did not cleanly separate thermal responses from chemotactic responses. Here we have isolated the thermal response by studying the behavior of single, tethered cells. The motor output of cells grown at 33degreesC was measured at constant temperature, from 10degrees to 40degreesC, and in response to small, impulsive increases in temperature, from 23degrees to 43degreesC. The thermal impulse response at temperatures < 31degreesC is similar to the chemotactic impulse response: Both follow a similar time course, share the same directionality, and show biphasic characteristics. At temperatures > 31degreesC, some cells show an inverted response, switching from warm- to cold-seeking behavior. The fraction of inverted responses increases nonlinearly with temperature, switching steeply at the preferred temperature of 37degreesC. 10.1073/pnas.0709903105 The thermal impulse response of Escherichia coli Eli Paster William Ryu doi:10.1073/pnas.0709903105 Proceedings of the National Academy of Sciences, Vol. 105, No. 14. 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