Retroactivity as a Criterion to Define Modules in Signaling Networks

Abstract

The concept of modularity has been widely studied in the context of molecular biology. Since engineering sciences are used to work in a modular manner, it is tempting to approach the definition of biological modules from an engineering perspective. From a system-theoretical point of view an interesting criterion might be the definition of modules where both the input signals and the output signals are unidirectional, that is, there is no retroactivity. In this chapter, we review the applicability of this concept to biological networks. We start describing which biochemical situations can lead to absence of retroactivity. Then, we show how this concept can be automatized into an algorithm to decompose biochemical networks into modules so that the retroactivity among the modules is minimized. This decomposition facilitates the analysis of complex models because the modules can, to some degree, be studied separately. We complement this analysis with a consideration of retroactivity in signal transduction processes using a domain-oriented description. Finally, we explore the interplay between retroactivity and thermodynamics in the domain-oriented description, and show how the binding site phosphorylation is a mechanism that is able to realize unidirectional signal transduction.