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Journal of Chemical Physics / Volume 132 / Issue 12 / COMMUNICATIONS
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J. Chem. Phys. 132, 121103 (2010); http://dx.doi.org/10.1063/1.3357980 (4 pages)

Communications: Hamiltonian regulated cell signaling network

Ge Wang1 and Muhammad H. Zaman2

1Department of Physics, The University of Texas at Austin, Austin, Texas 78712 USA
2Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA

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(Received 21 December 2009; accepted 17 February 2010; published online 29 March 2010)

Cell signaling is fundamental to cell survival and disease progression. Traditional approaches to study these networks have focused largely on probabilistic approaches, with a large number of ad hoc assumptions. In this paper, we develop a linear Hamiltonian model to study the integrin signaling network. The integrin signaling network is central to cell adhesion, migration, and differentiation, but has not been studied in the same detail as other cell cycle networks. In this study, the integrin signaling network with 16 nodes in thermal fluctuations is analyzed through ensemble averages on the linear Hamiltonian model. This new and analytically rigorous approach offers a quick method to find out the dominant nodes in the complex network, which operate in the thermal noise regime. The robust on/off transitions due to the different initial inputs also reflect the inherent structure in the network, providing new insights into structure and function of the network.

© 2010 American Institute of Physics

Article Outline

  1. INTRODUCTION
  2. HAMILTONIAN FOR CELL SIGNALING NETWORK
  3. FLUCTUATIONS OF INTERACTIONS
  4. SIGNIFICANT INPUTS
  5. CONCLUSION

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KEYWORDS and PACS

Keywords

cellular biophysics, complex networks, fluctuations, molecular biophysics, noise, physiological models, proteins, thermal noise

PACS

ARTICLE DATA

Digital Object Identifier
http://dx.doi.org/10.1063/1.3357980

PUBLICATION DATA

ISSN

0021-9606 (print)  
1089-7690 (online)

Publisher

$abstract.society.value is a Member of CrossRef American Institute of Physics

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Figures (4) Tables (1)

Figures (click on thumbnails to view enlargements)

FIG.1
The 16 nodes cell signaling network scheme. The relationship between each pair shows either the positive activating regulations (represented by arrow →) and the negative suppressing regulations (represented by a red cross ⊗).

FIG.1 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.2
The heat map shows the inherent structures of the integrin signaling network with parameters μ0 = 10 and σμ = 1. The vertical column on the corresponding node illustrates the possibility distribution between on(1) and off(0) states. The DNs, SDNs, and RNs are distinct by their statistical characteristics.

FIG.2 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.3
The free energy curve is normalized by kBT in the thermal fluctuation. The error bars shows the standard deviations due to the thermal noises.

FIG.3 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.4
The off/on transition for node Cas due to the different input states on FAK and Src. Five sets of data illustrate the thermal fluctuation effects.

FIG.4 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

Tables

Table I. The 16 nodes network is strongly robust even in the very chaotic thermal fluctuations. When the thermal fluctuation vary from 5% to 100% comparing to the mean value of the interaction strength μ0 = 10 (normalized in kBT), the deviations of nodes only change in a narrow range. So the classification of nodes is unchanged.

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