Design principles of signal transduction pathways to compensate intracellular perturbations

One of the great paradoxes in studying signal transduction pathways is their seemingly oversized topology. Even in rather small signalling cascades like MAP kinase it is unclear why so many kinase reactions are involved. Similarly one can show in bacterial chemotaxis that the topology can be simplified to arrive at almost perfect adaptation. These facts give the impression that signalling pathways are rather ‘tinkered’ than ‘properly engineered’, [1]. But the underlying assumption within this view on signalling pathways is the concept of ‘modularisation’ on one hand and moderate component tolerances on the other hand. Only these assumptions allow us to investigate signalling networks ignoring intra-cellular perturbations. In this work we show that the chemosensory pathway of E. coli is not only designed to transmit changes in ligand concentration to the flagella motor proteins under the condition of almost perfect adaptation, but also to resist intracellular perturbations.