CONICET | Buscador de Institutos y Recursos Humanos

Background. In a previous work we have presented the existence of a mechanism known as Pre-Equilibrium Sensing and Signaling (PRESS), which allows cells to discriminate between signaling levels that saturate receptors in equilibrium. This mechanism is based on the coupling between a slow and sustained detection module and a fast and transient response module. What results of PRESS is that certain signaling systems respond on a dose-dependent form, even for doses which saturates detection system in equilibrium, expanding the system?s dynamic range.Results. Previously, we haven?t considered membrane receptor trafficking, that is, internalizing and recycling processes. These processes are rarely considered, assuming that they happen in slower time scales than sensing and transduction of signals. However, PRESS mechanism requires slower sensing processes, what makes scales comparable. It is important, then, to consider these processes together and this is done in the current work.We have also analyzed cooperativity effects in membrane receptors with two binding sites. It is known that, in equilibrium, is not possible to distinguish between negative cooperativity and independent sites. Recent works show that pre-equilibrium information may allow to do so. We have studied in detail, with a combined theoretical/computational/statistical approach, the dynamics of cooperativity effects in the context of PRESS, in order to find measurable estimators for discrimination between these two microscopic scenarios.Conclusions. More realistic models of the sensing steps of signaling, represented by membrane receptors with cooperativity and trafficking processes, are capable of working in PRESS mode, suggesting that PRESS mechanism might be widespread.