Doctors have long known that hardening of the arteries, or atherosclerosis, typically appears at places where arteries split or bend. University of Virginia biomedical engineer Brian Helmke has set the stage for new treatments for this potentially deadly disease by showing how fluid turbulence within arteries produces chemical changes in cells lining blood vessels.
Combining 4-d microscopy and in vitro flow chambers lined with endothelial cells, Helmke is able to recreate the complicated flow patterns associated with arterial branch points and track changes in the shape of individual cells. He has discovered that these cells change shape as the direction of flow and pressure change and that the particular form these changes take are determined by the cell’s internal scaffolding.
“The cells didn’t necessarily deform at the point where we applied pressure,” Helmke says. “The forces were directed through the cell by its cytoskeleton to produce deformations elsewhere.” Deformations at these precise spots trigger a cascade of chemical activity within the cell that allows it to better withstand turbulence. For instance, one result of these changes is that cells remodel the sites where they adhere to the cell wall, increasing their stability. When Helmke changed the flow, he produced a different deformation and a different set of chemical reactions.
Helmke believes that when these processes go astray — for instance, when there is a defect in the cytoskeleton — a healthy response to turbulence is replaced by one that causes disease. Working backwards, he is trying to discover if he can prevent deformation by locking cells into an optimal grid of adhesion sites. With colleagues at U.Va., he is creating a material printed with a regular nanopattern of adhesion proteins. This work has implications, not only for understanding atherosclerosis, but also for creating more effective stents to open clogged arteries.
Helmke is an assistant professor in the U.Va. School of Engineering and Applied Science , Department of Biomedical Engineering. He holds degrees in bioengineering from the University of Pennsylvania and the University of California, San Diego. His research laboratory employs a multidisciplinary biomedical engineering approach to understand the relationship between intracellular mechanics and cell function. The lab is working on projects that bring together a joint biomedical engineering, materials science, and molecular biology approach to understanding cellular physiology.
By: Charlie Feigenoff
