UCSF

Neutrophils are one of the body's first lines of defense against pathogens. These cells can sense the molecular signatures of injury and infection and polarize their cytoskeletons in a single direction to move toward the sources of these cues. Previous work has detailed how these cells polarize toward signals, but it is just as important to understand how they adjust their direction over time. Neuroscientists have used virtual reality systems to understand how organisms process and respond to environmental information; we used optogenetics to perform comparable experiments in neutrophil-like HL-60 cells by controlling a key polarity signal in cells as they migrated. For example, by presenting cells with two polarity sites in various configurations, we tested which local features predicted the cell's preference for one stimulus compared to another. Using assays like this, we could tease apart which spatial and temporal characteristics of input signals controlled cell directionality. We found that the fronts of cells respond to the local rate-of-change in input signals and that the backs of cells are generally unresponsive. Migrating cells adjust direction based on where within the front they are experiencing the fastest increase in signal.