Cell surface receptors improve signaling properties when working far from steady-state: a numerical study

JUAN PABLO DI BELLA; ALEJANDRA VENTURA; ALEJANDRO COLMAN LERNER

Mar del plata

Congreso; 51va reunion anual de la sociedad argentina de bioquimica y biologia molecular (SAIB); 2015

SAIB

An important characteristic of every living cell is its ability to interpret correctly the surrounding environment. For this purpose, cells evolved sophisticated cellular signaling mechanisms that provide proper timely responses to environmental signals. Mathematical/computational modeling based on biological information can be used to improve our understanding of cellular signaling, thereby enhancing predictive accuracy.The first step in sensing extracellular information usually involves the reversible binding between an external ligand and a membrane receptor. We have shown in a recent publication that when cells are able to utilize of extracellular information before ligand-receptor binding reaches equilibrium, they are able to improve the range of ligand concentrations they can distinguish. We call this effect Pre-equilibrium Sensing and Signaling (PRESS)In this work we study how the properties of the ligand-receptor dose-response curve that allow PRESS affect a 2-state receptor model. In conclusion we found some limitiations for the ability of the receptor to dinstinguish high dosis (between 10 KD and 10000 KD) in pre-equilibrium conditions depending on the chemical reaction rates and the network model used for receptor ligand interaction.