Fluctuating signal and reversibility limit information and entropy in a MAPK signalling cascade

Intracellular signalling pathways act as communication channels that transmit information about the environment and enable cells to respond appropriately. The quantification of this information, along with the energetic cost involved, has therefore been an active area of research. The information transmitted, however, is often limited by the network architecture, noise and parameters or rate constants of the biochemical reactions involved in the pathway. In this work, therefore, we studied the well-known and ubiquitous mitogen-activated protein kinase (MAPK) pathway and showed that information transmission gets limited by introducing reversibility. In particular, we carried out stochastic simulations of two models of the MAPK system with a fluctuating ligand as the input and compared and contrasted the mutual information and energetic cost of the corresponding output, values of which are within the physiological range of MAPK systems studied experimentally. Furthermore, we also explored ways by which the pathway can optimize its functioning by adjusting its parameters, thereby, carrying out trade-offs between energy, fidelity and amplification.