Directional sensing and chemotaxis in eukaryotic cells - a quantitative study

Abstract

We investigate the mechanisms behind eukaryotic chemotaxis using the model organism Dictyostelium discoideum. We propose a theoretical model of directional sensing based on a local excitation/global inhibition mechanism, coupled to bistable chemical kinetics. The transition between the two stable states is driven by intracellular noise. Models of directional sensing are then tested experimentally by exposing individual D. discoideum to gradients and uniform concentrations of the chemoattractant cAMP, while monitoring the intracellular dynamics of PHCRAC-GFP, a marker of directional sensing. The gradients of cAMP are produced using a combination of photo-uncaging and microfluidics. In the last part of this work, the chemotactic motility of D. discoideum in linear profiles of cAMP is correlated with the signal to noise ratio of activated intracellular second messengers. For a better characterization of the chemotactic motility of wild-type and mutants cells, we use a Langevin equation whose parameters are retrieved from the experimental data to model chemotactic cell motion.