DYNAMICS OF GRADIENT SENSING IN SINGLE CELLS

Puerto Madryn

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

To choose a mating partner the yeast Saccharomycescerevisiae detects mating pheromones produced by yeast of theopposite sex using reversible binding to a GPCR. The non-motile yeast determine the direction of a potential matingpartner by measuring on which side there are more boundreceptors. This sensing modality can only work when externalpheromone does not saturate the receptors. However, thebehavior of yeast in dense mating mixtures indicates that, evenwhen pheromone concentration is much higher than theequilibrium constant of pheromone with its receptor, yeastpolarize in the correct direction. How might yeast accuratelydetermine gradients at high concentrations? Using a systemsbiology approach based on mathematical modeling andnumerical simulations we show thTo choose a mating partner the yeast Saccharomycescerevisiae detects mating pheromones produced by yeast of theopposite sex using reversible binding to a GPCR. The non-motile yeast determine the direction of a potential matingpartner by measuring on which side there are more boundreceptors. This sensing modality can only work when externalpheromone does not saturate the receptors. However, thebehavior of yeast in dense mating mixtures indicates that, evenwhen pheromone concentration is much higher than theequilibrium constant of pheromone with its receptor, yeastpolarize in the correct direction. How might yeast accuratelydetermine gradients at high concentrations? Using a systemsbiology approach based on mathematical modeling andnumerical simulations we show thTo choose a mating partner the yeast Saccharomycescerevisiae detects mating pheromones produced by yeast of theopposite sex using reversible binding to a GPCR. The non-motile yeast determine the direction of a potential matingpartner by measuring on which side there are more boundreceptors. This sensing modality can only work when externalpheromone does not saturate the receptors. However, thebehavior of yeast in dense mating mixtures indicates that, evenwhen pheromone concentration is much higher than theequilibrium constant of pheromone with its receptor, yeastpolarize in the correct direction. How might yeast accuratelydetermine gradients at high concentrations? Using a systemsbiology approach based on mathematical modeling andnumerical simulations we show that the actual bindingdynamics of pheromone to the receptor is such that enhancesgradient determination in near saturating conditions. We usedthe output of our simulations as input to a published model ofspontaneous emergence of cell polarity, and show that thepheromone binding dynamics results in significantly moreprecise polarization (in the direction of the gradient) than otherbinding rates. Our results apply to other biological systems insimilar binding dynamics.at the actual bindingdynamics of pheromone to the receptor is such that enhancesgradient determination in near saturating conditions. We usedthe output of our simulations as input to a published model ofspontaneous emergence of cell polarity, and show that thepheromone binding dynamics results in significantly moreprecise polarization (in the direction of the gradient) than otherbinding rates. Our results apply to other biological systems insimilar binding dynamics.at the actual bindingdynamics of pheromone to the receptor is such that enhancesgradient determination in near saturating conditions. We usedthe output of our simulations as input to a published model ofspontaneous emergence of cell polarity, and show that thepheromone binding dynamics results in significantly moreprecise polarization (in the direction of the gradient) than otherbinding rates. Our results apply to other biological systems insimilar binding dynamics.