  Macromolecules occupy between 34 and 44% of the cell cytoplasm, about half
the maximum pack- ing density of spheres in three dimension. Yet, there is no
clear understanding of what is special about this value. To address this
fundamental question we investigate the effect of macromolecular crowding on
cell metabolism. We develop a cell scale flux balance model capturing the main
features of cell metabolism at different nutrient uptakes and macromolecular
densities. Using this model we show there are two metabolic regimes at low and
high nutrient uptakes. The latter regime is charac- terized by an optimal
cytoplasmatic density where the increase of reaction rates by confinement and
the decrease by diffusion slow-down balance. More important, the predicted
optimal density is in the range of the experimentally determined density of E.
coli. We conclude that cells have evolved to a cytoplasmatic density resulting
in the maximum metabolic rate given the nutrient availability and
macromolecular crowding effects and report a flux balance model accounting for
its effect.
