Dynamics of gradient sensing in single cells

ALEJANDRA C VENTURA; MATIAS GOLDIN; ALAN BUSH; ARIEL CHERNOMORETZ; ALEJANDRO COLMAN-LERNER

Conferencia; 46th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2010

To choose a mating partner the yeast Saccharomyces cerevisiaedetects mating pheromones produced by yeast of the opposite sexusing reversible binding to a GPCR. The non-motile yeast determinethe direction of a potential mating partner by measuring on whichside there are more bound receptors. This sensing modality can onlywork when external pheromone does not saturate the receptors.However, the behavior of yeast in dense mating mixtures indicatesthat, even when pheromone concentration is much higher than theequilibrium constant of pheromone with its receptor, yeast polarizein the correct direction. How might yeast accurately determinegradients at high concentrations? Using a systems biology approachbased on mathematical modeling and numerical simulations weshow that the actual binding dynamics of pheromone to the receptoris such that enhances gradient determination in near saturatingconditions. We used the output of our simulations as input to apublished model of spontaneous emergence of cell polarity, andshow that the pheromone binding dynamics results in significantlymore precise polarization (in the direction of the gradient) than otherbinding rates. Our results apply to other biological systems in similarbinding dynamics.