A diffusion-translocation model for gradient sensing by chemotactic cells.

Small chemotactic cells like Dictyostelium and neutrophils transduce shallow spatial chemoattractant gradients into strongly localized intracellular responses. We show that the capacity of a second messenger to establish and maintain localized signals, is mainly determined by its dispersion range, lambda = the square root of D(m)/k(-1), which must be small compared to the cell's length. Therefore, short-living second messengers (high k(-1)) with diffusion coefficients D(m) in the range of 0-5 microm(2) s(-1) are most suitable. Additional to short dispersion ranges, gradient sensing may include positive feedback mechanisms that lead to local activation and global inhibition of second-messenger production. To introduce the essential nonlinear amplification, we have investigated models in which one or more components of the signal transduction cascade translocate from the cytosol to the second messenger in the plasma membrane. A one-component model is able to amplify a 1.5-fold difference of receptor activity over the cell length into a 15-fold difference of second-messenger concentration. Amplification can be improved considerably by introducing an additional activating component that translocates to the membrane. In both models, communication between the front and the back of the cell is mediated by partial depletion of cytosolic components, which leads to both local activation and global inhibition. The results suggest that a biochemically simple and general mechanism may explain various signal localization phenomena not only in chemotactic cells but also those occurring in morphogenesis and cell differentiation.