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Berkeley scientists find new way to get physical in the fight against cancer
Date:3/11/2010

mmalian cells are sensitive to the physical aspects of their environment, such as the texture or geometry of the surrounding tissue. However, evidence that physical forces impact freely-moving signaling molecules (as opposed to focal adhesion molecules) in the membranes of cells has been lacking because the cell membrane is an environment that has always been difficult to characterize and manipulate. Groves and his research group have found a way to overcome this obstacle with the development of unique synthetic membranes constructed out of lipids and assembled onto a substrate of solid silica that enables them to directly control cellular signaling activities.

"We call this approach the 'spatial mutation' strategy because molecules in a cell can be spatially re-arranged without altering the cell in any other way," Groves says. "We first used this strategy in 2005 to study T cell signaling in the immune system."

In this latest study, Groves and his colleagues worked with mammary epithelial cells from a library of 26 model human breast cancer cell lines that have been well-characterized by co-author Gray and his research groups at Berkeley Lab and UC San Francisco.

Says co-author Nair, "Gray's research has demonstrated that this library substantially reproduces the genomic abnormalities and drug responsiveness of primary breast cancer tumor cells from patients, and constitutes the most comprehensive system for the study of the various aberrations responsible for human breast cancer."

To test the sensitivity of the EphA2/ephrin-A1 signaling complex to mechanical forces, Groves and his group patterned their silica substrates with chromium metal lines that were 10 nanometers in height and 100 nanometers wide. These metal lines acted as diffusion barriers that impeded the lateral mobility of the EphA2/ephrin-A1 complexes in the synthetic membrane. The movement and spatial organization of the complexes were subsequently tracked throug
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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