Origins of cell-to-cell variability, kinetic proof-reading and the robustness of MAPK signal transduction
Many biological, physical, and social interactions have a particular dependence on where they take place. In living cells, protein movement between the nucleus and cytoplasm affects cellular response (i.e., proteins must be present in the nucleus to regulate their target genes). Here we use recent developments from dynamical systems and chemical reaction network theory to identify and characterize the key-role of the spatial organization of eukaryotic cells in cellular information processing. In particular the existence of distinct compartments plays a pivotal role in whether a system is capable of multistationarity (multiple response states), and is thus directly linked to the amount of information that the signaling molecules can represent in the nucleus. Multistationarity provides a mechanism for switching between different response states in cell signaling systems and enables multiple outcomes for cellular-decision making. We find that introducing species localization can alter the capacity for multistationarity and mathematically demonstrate that shuttling confers flexibility for and greater control of the emergence of an all-or-none response.