The importance of constraints and four general categories of constraints were described in Chapter 16. The formal imposition of constraints to form a solution space containing all candidate functional states of networks was discussed in Chapter 12. There are clearly a multitude of constraints that cellular functions have to abide by. In this chapter we discuss constraints in more detail, how they are defined, understood and described.

Genome-scale Viewpoints

Crowded and interconnected A cell is faced with myriad constraints on its integrated functions. The cell is a very crowded place that is packed with various types of molecules. These molecules have to have certain biochemical states (such as being properly phosphorylated or methylated), cellular location, and abundance to ensure proper overall function of a cell. The genome-scale biophysical and network view of an E. coli cell illustrates these features (Figure 17.1). Similar renderings of other cell types convey a similar picture [146–148]. At the biochemical level, these components interact chemically through chemical transformations or associations of molecules to form aggregates. The former represent the formation or breakage of covalent bonds, while the latter is based on intermolecular forces, such as those that lead to hydrogen bonds. The number of such biochemical interactions is large (Figure 17.1B). Thus the cell is crowded, that means all sorts of topological constraints and steric hindrances, and interconnected, that means all sorts of constraints on network functions.

Range of acceptable parameter values In the case of bacteria, all these processes take place simultaneously in a volume that is on the order of a cubic micron. Given the large number of constraints that govern cellular functions, it is surprising that numerical values exist for all the physical constants that allow coherent cellular functions. Thus, some scientists consider the living process to be highly improbable.