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Biologists Find Key Mechanism
Regulating Cell Movement
September 6, 1999

ow cells move is a question that has perplexed biologists for more than a century. Without an explanation, we lack a fundamental understanding of the controlled cell movement involved in wound healing and the uncontrolled cell movement involved with diseases like metastatic cancer.

Now a team of UConn biologists and colleagues, investigating the role calcium plays in cell movement, has discovered a mechanism by which cells convert physical stimuli into biochemical signals that can power cell locomotion. The finding eventually could result in new treatments for wounds and diseases such as cancer, the researchers say. A report on their findings appears in the July 22 issue of the journal Nature.

"Basic research into cell locomotion is very important because it helps us understand wound healing, the movement of cancer cells, our immune system and the development of human and animal embryos," says Juliet Lee, assistant professor of molecular and cell biology, and lead author of the Nature article, who came to UConn in 1998. "When we learn to control cell movement, we can have a major positive impact on a host of medical problems."

Biologists have known that calcium ions in a cell regulate many of the molecular processes that are essential for cell movement, but it has remained unclear how calcium regulates overall cell movement. To investigate that role, the researchers conducted a complicated series of experiments involving stretching fish scale cells called keratocytes on elastic rubber sheets. During stretching, they used video microscopy - a technique that marries microscopes with television cameras - to continuously monitor the entry of calcium ions into the cells in response to the stretching. They also employed a technique called patch clamp, that allowed them to stretch the cells while electrically measuring the flow of calcium ions into the cell.

The researchers discovered that calcium concentrations inside the cells increased for periods of three to five seconds when they became temporarily "stuck" on the rubber surface they were crawling over, or when the researchers mechanically stretched the cell by stretching the rubber surface.

They also found that the calcium increases came from calcium channels activated when the cells were stretched. The calcium influx, in turn, induced the cell to detach itself when stuck, or re-form its shape away from the direction of stretching.

The so-called "stretch-activated calcium channels" provide an explanation for the mechano-chemical regulation of cell movement and could account for the calcium signals measured in moving cells. Many other cell types contain stretch-activated calcium channels, and the researchers believe they may represent a general mechanism by which cell movement is controlled in those cells as well.

"This is the first research to demonstrate that stretch-activated calcium channels regulate motility," says Barry Johnson, assistant professor of physiology and neurobiology at UConn and co-author of the article in Nature. "No one knew or considered they were involved in cell movement."

The research is a collaboration between biologists at UConn and the University of North Carolina at Chapel Hill.

David Bauman