Traveling wave chemotaxis of neutrophil-like HL-60 cells

Abstract The question of how changes in chemoattractant concentration translate into the chemotactic response of immune cells serves as a paradigm for the quantitative understanding of how cells perceive and process temporal and spatial information. Here, using a microfluidic approach, we analyzed the migration of neutrophil-like HL-60 cells to a traveling wave of the chemoattractants fMLP and leukotriene B4 (LTB4). We found that under a pulsatile wave that travels at a speed of 95 and 170 µm/min, cells move forward in the front of the wave but slow down and randomly orient at the back due to temporal decrease in the attractant concentration. Under a slower wave, cells re-orient and migrate at the back of the wave; thus, cell displacement is canceled out or even becomes negative as cells chase the receding wave. FRET-based analysis indicated that these patterns of movement correlated well with spatiotemporal changes in Cdc42 activity. Furthermore, pharmacological perturbations suggested that migration in front of the wave depends on Cdc42, whereas that in the back of the wave depends more on PI3K/Rac and ROCK. These results suggest that pulsatile attractant waves may recruit or disperse neutrophils, depending on their speed and degree of cell polarization. Significance statement The way neutrophil chemotaxis is directed by attractants is thought to depend on temporal and spatial concentration changes, however the response to a transient pulsatile stimulus has not been well explored. A moderately fast traveling wave of fMLP and leukotrieneB4 (LTB4) directs unidirectional cell migration. Under slow waves, cells respond to the back of the wave; thus, cell displacement is canceled out. Cdc42, PI3K, Rac, and ROCK contributed differently to responses at the front and back of the wave. These findings suggest that traveling waves of attractant can guide immune cell recruitment and dispersal.