Dynamics of gradient sensing in single cells

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

Punta Ballena

Simposio; Yeast Systems Biology Symposium; 2011

Institut Pasteur de Montevideo

To choose a mating partner the yeast Saccharomyces cerevisiae detects mating pheromones produced by yeast of the opposite sex using reversible binding to a GPCR. The non-motile yeast determine the direction of a potential mating partner by measuring on which side there are more bound receptors. This sensing modality can only work when external pheromone does not saturate the receptors. However, the behavior of yeast in dense mating mixtures indicates that, even when pheromone concentration is much higher than the equilibrium constant of pheromone with its receptor, yeast polarize in the correct direction. How might yeast accurately determine gradients at high concentrations? Using a systems biology approach based on mathematical modeling and numerical simulations we show that the actual binding dynamics of pheromone to the receptor is such that enhances gradient determination in near saturating conditions. We used the output of our simulations as input to a published model of spontaneous emergence of cell polarity, and show that the pheromone binding dynamics results in significantly more precise polarization (in the direction of the gradient) than other binding rates. Our results apply to other biological systems with similar binding dynamics.