Mathematical modeling and experimental validation of chemotaxis under controlled gradients of methyl-aspartate in Escherichia coli

Abstract

Escherichia coli has evolved an intracellular pathway to regulate its motion termed as chemotaxis so as to move towards a favorable environment such as regions with higher concentration of nutrients. Chemotaxis is a response to temporal and spatial variation of extracellular ligand concentration and randomness in motion induced by collisions with solvent molecules. Previous studies have reported average drift velocities for a given gradient and do not measure drift velocities as a function of time and space. To address this issue, a novel experimental technique was developed to quantify the motion of E. coli cells to varying concentrations and gradients of methyl-aspartate so as to capture the spatial and temporal variation of the drift velocity. A two-state receptor model accounting for the intracellular signaling pathway predicted the experimentally observed increase in drift velocity with gradient and the subsequent adaptation. Our study revealed that the rotational diffusivity induced by the extracellular environment is crucial in determining the drift velocity of E. coli. The model predictions matched with experimental observations only when the response of the intracellular pathway was highly ultra-sensitive to overcome the extracellular randomness. The parametric sensitivity of the pathway indicated that the dissociation constant for the binding of the ligand and the rate constants of the methylation/demethylation of the receptor are key to predict the performance of the chemotactic behavior. The study also indicates a possible role of oxygen in the chemotaxis response and that the response to a ligand may have to account for effects of oxygen.