Bound attractant at the leading vs. the trailing edge determines chemotactic prowess

Abstract
We have analyzed chemotaxis of neutrophil-differentiated HL60 cells in microfluidic devices that create exponential gradients of the chemoattractant, f-Met-Leu-Phe (fMLP). Such gradients expose each cell to a difference in fMLP concentration (ΔC) across its diameter that is directly proportional to the ambient concentration (C) at that cell's position in the gradient, so the ratio ΔC/C is constant everywhere. Cells exposed to ambient fMLP concentrations near the constant of dissociation (K d) for fMLP binding to its receptor (≈10 nM) crawl much less frequently when ΔC/C is 0.05 than when it is 0.09 or 0.13. Hence, cells can detect the gradient across their diameter without moving and, thus, without experiencing temporal changes in attractant concentration. At all ΔC/C ratios tested, the average chemotactic prowess of individual cells (indicated by the distance a cell traveled in the correct direction divided by the length of its migration path) is maximal for cells that start migrating at concentrations near the K d and progressively decreases at higher or lower starting concentrations.