1 8 | L E H I G H B U L L E T I N R E S E A R C H Full Sail Ahead NIH grant funds researchers’ exploration of lipid membranes Damien Thévenin COLLABORATION Aurelia Honerkamp-Smith, assistant professor of physics, and Damien Thévenin, associate professor of chemistry, envision the models they produce will apply to multiple cell lines and fow conditions and will lay the groundwork for future research directions. Two Lehigh researchers have been awarded a fve-year, $1.5 million grant from the National Institutes of Health to examine lipid membranes and the method in which lipids and proteins travel in response to fuid fow. Aurelia Honerkamp-Smith, assistant professor of physics, and Damien Thévenin, associate professor of chemistry, also will test whether fow transport of a membrane protein triggers intracellular signaling in endothelial cells. In blood vessels, the manner in which cells fow through their environment regulates processes such as blood pressure, bone density and neural growth. Yet, the molecular factors behind fow mechanotransduction, the processes through which cells sense and respond to mechanical stimuli by converting them to biochemical signals, remain unclear. Endothelial cells are found on the inside of blood vessels, and Honerkamp-Smith and Thévenin are investigating a process that occurs when these cells feel a fow. They hope to identify the fundamental principles that govern fow transport of membrane-linked proteins in model membranes and develop a model that predicts protein motion in physiological situations. When endothelial cells feel fow, they quickly start to produce nitrous oxide. The researchers will explore how the fow-mediated lateral transport of glypican-1 initiates this short-term fow response in endothelial cells. They also will consider how lipid sorting by fow contributes to fow signaling in their model system and living cell membranes. What’s interesting, says Honerkamp-Smith, is that glypican is located on the outside of the cell, and it is unknown how it activates the nitrous oxide synthase on the inside. She theorizes that physiologically signifcant protein and lipid concentration gradients arise from interactions between fuid fow and complex membranes. That hypothesis is based on the premise that extracellular lipid-anchored proteins such as glypican-1 can be transported along the plasma membrane by external fow, with the aqueous portion of the protein acting as a molecular sail. “With this particular protein, its structure is such that it is really good at acting like a little sailboat. … With this funding, we can try to fgure out whether it is actually the lateral movement of the protein that is activating the fow response instead of some other type of interaction,” Honerkamp-Smith says. Studying a series of proteins produced by genetic manipulation in the Thévenin lab will allow the researchers to determine how altering the proteins changes their function. “We buildmodel proteins with increasing complexitywith different membrane anchors and sizes that can be analyzed in vitro or directly in cells," Thévenin says. "Aurelia's lab then measures how they fow and analyzes the results based on fuid physics. “This systematic approach allows us to frst understand the basic principles behind protein transport on the cell membrane. Our main goal is to link this lateral movement to signaling events inside cells and changes in cell response. … It is not easy to test experimentally but it makes the overall project even more stimulating and highlights the importance of collaborative work in addressing exciting and impactful questions.” —Rob Nichols
RkJQdWJsaXNoZXIy MTA0OTQ5OA==