(761a) Dynamic Microfluidic Platform to Analyze the Effects of Spatiotemporal Gradient Changes On Neutrophil Chemotaxis

Neutrophils constitute the largest class of white blood cells and play a vital role in the innate immune response.  These cells sense and migrate up concentration gradients toward sites of infection and inflammation in a process known as chemotaxis. In vivo, many cell types respond to infection and inflammation, creating a complex and constantly changing multiple chemoattractant landscape.  Much is known of the signaling pathways and molecular interactions that regulate neutrophil response to a single static chemical cue. And while work has begun to elucidate cellular response to multiple static cues, little is known about the effect of dynamic changes in gradients on cellular response.

Previous dynamic microfluidic platforms have studied the temporal responses of neutrophil chemotaxis to changes in the concentration gradients of a single gradient [1].  We propose to examine neutrophil response to spatiotemporal changes in multiple chemoattractant gradients.  Using a combination of chemoattractants, such as those produced near the source of infection (end-target chemoattractants) and those produced by inflamed host cells (endogenous intermediary chemoattractants), a dynamically changing microenvironment similar to that in vivo can be studied.

The goal of this work is to understand how neutrophils integrate and prioritize dynamically changing chemoattractant gradients.  By analyzing neutrophil migration in response to changes in the multiple chemoattractant landscape (fMLP, IL8, and LTB4), we can begin to unravel how neutrophils respond to highly complex chemoattractant landscapes.

Reference

1. Irimia, D., Liu, S., et al.  Microfluidic system for measuring neutrophils migratory responses to fast switches of chemical gradients.  Lab on a Chip 6(2006).