Bound attractant at the leading vs. the trailing edge determines chemotactic prowess.
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 (DeltaC) across its diameter that is directly proportional to the ambient concentration (C) at that cell's position in the gradient, so the ratio DeltaC/C is constant everywhere. Cells exposed to ambient fMLP concentrations near the constant of dissociation (K(d)) for fMLP binding to its receptor ( approximately 10 nM) crawl much less frequently when DeltaC/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 DeltaC/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.
Herzmark
Paul
P
Departments of Cellular and Molecular Pharmacology, University of California, 600 16th Street, San Francisco, CA 94158, USA.
Campbell
Kyle
K
Wang
Fei
F
Wong
Kit
K
El-Samad
Hana
H
Groisman
Alex
A
Bourne
Henry R
HR
D002633:Chemotaxis / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology
D009240:N-Formylmethionine Leucyl-Phenylalanine