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Sci. Signal., 28 July 2009
Vol. 2, Issue 81, p. pe46
[DOI: 10.1126/scisignal.281pe46]


The Complexity of Cell Signaling and the Need for a New Mechanics

William S. Hlavacek1,2 and James R. Faeder3*

1 Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
2 Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
3 Department of Computational Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.

Abstract: Cell signaling systems respond to multiple inputs, such as ligands of cell-surface receptors; and produce multiple outputs, such as changes in gene expression and cellular activities, including motility, proliferation, and death. This "macroscopic" input-output behavior is generated by a web of molecular interactions that can be viewed as taking place at a lower, "microscopic" level. These interactions prominently involve posttranslational modification of proteins and the nucleation of protein complexes. Behaviors at both the micro- and macroscopic levels are complex and must be probed systematically and characterized quantitatively as a prelude to the development of a predictive understanding of a cell signaling system. We must also have a theoretical framework or a mechanics within which we can determine how macroscopic behaviors emerge from known microscopic behaviors or change with manipulations of microscopic behaviors. To connect behaviors at both levels, we suggest that a new mechanics is now required. Newly available data support the idea that this mechanics should enable one to track the site-specific details of molecular interactions in a model, such as the phosphorylation status of individual amino acid residues within a protein.

* Corresponding author. E-mail, faeder{at}

Citation: W. S. Hlavacek, J. R. Faeder, The Complexity of Cell Signaling and the Need for a New Mechanics. Sci. Signal. 2, pe46 (2009).

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