Microfluidic Gradient Platforms: Tools to Understand Immune Cell Behavior

Neutrophils are the most abundant immune cell type that form an integral part of body’s defense system. These cells efficiently sense and migrate up concentration gradients of chemical attractants toward sites of infection in a process termed chemotaxis. Such chemoattractants include end-target chemoattractants produced by bacteria or pathogens, as well as intermediary chemoattractants produced by inflamed host tissues. While much is known about the molecular interactions and signaling pathways that regulate cellular responses to individual signals, little is known about how cells process multiple signals to effect migration in the appropriate direction.

The goal of this work is to investigate how neutrophils integrate and prioritize multiple chemotactic signals to navigate toward bacteria and pathogens in vivo. To this end, we investigated neutrophil migration in response to multiple chemoattractant gradients generated using laminar flow-based platforms. By analyzing the migration behavior of neutrophils in microfluidic gradient platforms, we have begun to elucidate their response in multiple chemotactic signals. Our experiments reveal distinctive oscillatory behavior of neutrophils in multiple chemoattractant gradients. The chemotactic response of cells suggests the role of directional persistence and cellular memory in guiding cells effectively to their targets. These results provide insight into a key component of the inflammatory response and should aid in the design of novel immunotherapeutic strategies.