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 (Kd) 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 Kd and progressively decreases at higher or lower starting concentrations. © 2007 by The National Academy of Sciences of the USA.