FAR FROM STEADY-STATE CELL RECEPTORS EXHIBIT IMPROVED SIGNALING PROPERTIES: A NUMERICAL STUDY

JUAN PABLO DI BELLA; ALEJANDRA C VENTURA; ALEJANDRO COLMAN-LERNER

Mar del Plata

Conferencia; 51 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

SAIB

Sensing extracellular information often involves binding of a ligand to a receptor. We have shown that cells able respond to ligands before they reach binding equilibrium are able to discriminate ligand concentrations otherwise indistinguishable. We call this effect Pre-equilibrium Sensing and Signaling (PRESS). Here we study PRESS using amore realistic receptor model that considers a reversible isomerization between active and inactive states, each of which may bind the ligand. We found that this model can do PRESS, except for the case in which binding mostly occurs with the active state of the receptor. In this case, fast binding would reduce the availability of pre-equilibriuminformation even when preceded by slow isomerization step. On the other hand, if the reaction rates are such that the activation pathway undergoes a fast binding process followed by a slower activation of the bound receptor, PRESS occurs but in a limited range of doses. Our computational study allows for identifiability of conditions (relationshipsbetween kinetic rates) necessary for this system to improve its sensing capabilities around a given dose range and using a certain time window.