TY - JOUR T1 - The Complexity of Cell Signaling and the Need for a New Mechanics JF - Science Signaling JO - Sci. Signal. SP - pe46 LP - pe46 DO - 10.1126/scisignal.281pe46 VL - 2 IS - 81 AU - Hlavacek, William S. AU - Faeder, James R. Y1 - 2009/07/28 UR - http://stke.sciencemag.org/content/2/81/pe46.abstract N2 - 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. ER -