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

Cell signaling systems respond to multiple inputs, such as ligands of cellsurface 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.