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Properties Of A Multidimensional Landscape Model For Determining Cellular Network Thermodynamics

Hubbard, J. B.; Halter, M.; Plant, A. L.

2019-06-26 systems biology
10.1101/682690 bioRxiv
Show abstract

The steady state distributions of phenotypic responses within an isogenic population of cells result from both deterministic and stochastic characteristics of biochemical networks. A biochemical network can be characterized by a multidimensional potential landscape based on the distribution of responses and a diffusion matrix of the correlated dynamic fluctuations between N-numbers of intracellular network variables. The Boltzmann H-function defines the rate of free energy dissipation of a network system and provides a framework for determining the heat associated with the nonequilibrium steady state and its network components. We conjecture that there is an upper limit to the rate of dissipative heat produced by a biological system, and we show that the dissipative heat has a lower bound. The magnitudes of the landscape gradients and the dynamic correlated fluctuations of network variables are experimentally accessible, and through an analysis that we refer to as Thermo-Fokker-Planck (Thermo-FP), provide insight into the composition of the network and the relative thermodynamic contributions from network components. We surmise that these thermodynamic quantities allow determination of the relative importance of network components to overall network control.

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