"We normally think of cells responding to mechanical forces at their periphery," Burridge said. "This is the first time, I think, that someone has shown that an isolated organelle can respond to mechanical force. I think it is actually a significant finding in the big picture of biology."
In the Journal of Immunology paper, lead author graduate student Elizabeth Lessey-Morillon examined the ways in which the cells lining our blood vessels stiffen and relax to allow immune system cells to pass out of the bloodstream into surrounding tissue. Cancer researchers have a particular interest in this process, as metastasizing tumor cells may use the same mechanisms to migrate through the body.
"We think metastasizing cells may essentially mimic what white blood cells do," said Burridge.
Using magnetic beads attached to the endothelial cells that line blood vessels, Lessey-Morillon discovered that applying force to the cells caused them to stiffen, opening gaps between the cells through which the white blood cells could pass. The response activated a pathway mediated by the proteins RhoA and LARG.
When she blocked the pathway, the cell stiffening response slowed. Because the pathway may also play a role in cancer metastasis, Burridge said the response could indicate that this pathway could be a viable target for future therapies.
"We think this response would be true also for tumor cells moving over the surface. They wouldn't be as competent in passing through the endothelial wall," said Burridge.
|Contact: William Davis|
University of North Carolina Health Care