CONICET | Buscador de Institutos y Recursos Humanos

Sensing extracellular changesinitiates signal transduction and is the first stage of cellulardecision-making. Ligand binding to cell membrane receptors is a key event inthose sensing stages. It is rarely certain whether cellular responses arerelated to initial changes in receptor binding or to the level of receptorbinding achieved at some later time, but it is likely that the dynamics ofreceptor/ligand binding contributes significantly to the dynamics of theresponse. Particularly, certain properties of the sensing steps are usuallycharacterized in equilibrium, like the value of half-maximal effectiveconcentration, the dynamic range, and the Hill coefficient. However, if thetime constant of downstream signal transduction steps is shorter than that ofligand-receptor binding, those properties should be evaluated inpre-equilibrium. Using a simple monovalent bindingmodel, a two-state binding model, and two limiting cases of this last one inwhich only one receptor form can bind or release ligand, we studied thementioned properties in pre-equilibrium. We combined analytical tools whenpossible, with computational modeling and parameter space exploration. Our results imply that pre-equilibrium sensing ispossible depending on the relation of binding and activation rates. Whenbinding rates are slower than activation rates, the system can sense high doseconcentrations on pre-equilibrium. Conversely, when binding is faster thanactivation, pre-equilibrium sensing properties remains similar than steadystate properties. Moreover, when the time scales are similar, pre-equilibriumsensing is possible but with certain limitations, depending on the timeconstant and the ligand concentration involved on the downstream process.