A diffusion-translocation model for gradient sensing by chemotactic cells

Small chemotactic cells like Dictyostelium and neutrophils transduce shallo w spatial chemoattractant gradients into strongly localized intracellular r esponses. We show that the capacity of a second messenger to establish and maintain localized signals, is mainly determined by its dispersion range, l ambda = rootD(m)/k(-1), which must be small compared to the cell's length. Therefore, short-living second messengers (high k(-1)) with diffusion coeff icients D-m in the range of 0-5 mum(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-me ssenger production. To introduce the essential nonlinear amplification, we have investigated models in which one or more components of the signal tran sduction cascade translocate from the cytosol to the second messenger in th e plasma membrane. A one-component model is able to amplify a 1.5-fold diff erence of receptor activity over the cell length into a 15-fold difference of second-messenger concentration. Amplification can be improved considerab ly by introducing an additional activating component that translocates to t he membrane. In both models, communication between the front and the back o f the cell is mediated by partial depletion of cytosolic components, which leads to both local activation and global inhibition. The results suggest t hat a biochemically simple and general mechanism may explain various signal localization phenomena not only in chemotactic cells but also those occurr ing in morphogenesis and cell differentiation.