IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cell surface receptors modify their signaling properties when working far from steady-state: a mathematical/computational study
Autor/es:
JUAN PABLO DI BELLA; ALEJANDRA C VENTURA; ALEJANDRO COLMAN-LERNER; FEDERICO SEVLEVER
Lugar:
Buenos Aires
Reunión:
Conferencia; Frontiers in Physical Sciences; 2016
Institución organizadora:
ICAS
Resumen:
Sensing extracellular changes initiates signal transduction and is the first stage of cellulardecision-making. Ligand binding to cell membrane receptors is a key event in those sensingstages. It is rarely certain whether cellular responses are related to initial changes in receptorbinding or to the level of receptor binding achieved at some later time, but it is likely that thedynamics 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 Hillcoefficient. However, if the time constant of downstream signal transduction steps is shorterthan 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 casesof this last one in which only one receptor form can bind or release ligand, we studied thementioned properties in pre-equilibrium, finding that the dynamic range of a signalingpathway can be modulated (shifted or enlarged) by using pre-equilibrium properties of theligand-receptor reaction. We combined analytical tools when possible, with computationalmodeling and parameter space exploration. We have also analyzed cooperativity effects inmembrane receptors with two binding sites. It is known that, in equilibrium, is not possible todistinguish between negative cooperativity and independent sites. Recent works showed thatpre-equilibrium information may allow to do so. We have studied in detail the dynamics ofcooperativity effects in order to find measurable estimators for discrimination between thesetwo microscopic scenarios.