Sensing Microsystems for Decoding Cellular Communications

Alexander Revzin and Yadong Gao from the University of California Davis are supported by an award from the Nano-Biosensing Program to develop sensing microsystems for investigating the communication between liver cells in cases of injury by toxic substances or infection. Signaling between nearby cells is involved in inflammation responses and ultimately their damage or death, but there remains uncertainty of what is cause and what is effect. This work is to unravel the different aspects of signaling between liver cells in a laboratory-on-a-chip environment with appropriate sensing capabilities built in. The techniques and devices to be developed are expected to have benefits for other problems in biology with complex cellular communications that need to be unraveled, e.g., wound healing, fibrosis and so on. A diverse group of undergraduate and graduate students and post doctoral fellows are being trained in this project.

Paracrine signaling is particularly relevant in the liver where an injury triggers a complex combination of paracrine signals including inflammatory and fibrogenic cytokines/growth factors. Recent findings suggest that, under toxication or infection, hepatocytes may not be simple victims of stromal-cell/macrophage inflammatory signals but may be active participants in and possibly triggers of the signaling in the liver. The understanding of cellular communications remains limited because the tools for discerning where and when secreted signals appear and how they affect neighboring cells are not available. This project is working to answer this need by developing novel biosensors and microfluidic devices for dissecting cellular communication. These incorporate multiplexed aptasensors for detection of several cell-secreted inflammatory cytokines in parallel as well as reconfigurable microfluidics utilizing valves to control how and when different liver cell types communicate on chip. There are several questions for which technological solutions are being sought: How may cell secreted factors be dynamically monitored? How may sensors be regenerated for simultaneous detection of several cell-secreted factors? How may originating and responding signals be recognized when two cell types are present? How do secretion rates change during heterotypic cellular communications? This work aims at deeper understanding of cell- and tissue-level responses to liver disease or injury and identification of cellular targets and temporal windows for treatment. Because cellular interactions in the local microenvironment are important throughout biology, the tools being developed will be widely applicable.