From networks to systems to complex systems: A signaling pathway coordination case study

Networks of signaling pathways provide a robust mechanism for cells to respond to various biological stimuli. In this paper we demonstrate cell adaptation through the viewpoint of an organizing principle between two interconnected pathways- MAPK and PKC. We use a multi-layered system representation of the pathways to determine the pathway components contributing to the adaptive behavior and coordination. The adaptation can be thought of as being manifested by a change in parameters of the coordinator. In silico experiments are conducted using MAPK/PKC mathematical model in literature to investigate the role of PLA₂ as a coordinator is reported here. Our results show that varying parameters of the coordinator not only activates the network of pathways where otherwise the pathway activity is very low, but also reveal the ability of the system to activate itself in the absence of the input, indicating relevance of the principle of bounded autonomy.