CONICET | Buscador de Institutos y Recursos Humanos

Sensing extracellular changes initiates signal transduction and is the first stage of cellular decision-making. Ligand binding to cell membrane receptors is a key event in those sensing stages. It is rarely certain whether cellular responses are related to initial changes in receptor binding or to the level of receptor binding achieved at some later time, but it is likely that the dynamics of receptor/ligand binding contributes significantly to the dynamics of the response. Particularly, certain properties of the sensing steps are usually characterized in equilibrium, like the value of half-maximal effective concentration, the dynamic range, and the Hill coefficient. However, if the time constant of downstream signal transduction steps is shorter than that of ligand-receptor binding, those properties should be evaluated in pre-equilibrium.Using a simple monovalent binding model, a two-state binding model, and two limiting cases of this last one in which only one receptor form can bind or release ligand, we studied the mentioned properties in pre-equilibrium. We combined analytical tools when possible, with computational modeling and parameter space exploration.Our results imply that pre-equilibrium sensing is possible depending on the relation of binding and activation rates. When binding rates are slower than activation rates, the system can sense high dose concentrations on pre-equilibrium. Conversely, when binding is faster than activation, pre-equilibrium sensing properties remains similar than steady state properties. Moreover, when the time scales are similar, pre-equilibrium sensing is possible but with certain limitations, depending on the time constant and the ligand concentration involved on the downstream process.