A funny thing happens to red blood cells when they’re stored outside the body. The normally flat, disk-shaped cells puff into spiky balls. Put them back in the bloodstream later and they revert to their normal shape. Recently, Notre Dame chemists learned how to flip the spiky cells back to the disk shape in the test tube. That bit of chemical wizardry may seem insignificant, but it could lead to the development of powerful new anti-cancer drugs, says Professor of Chemistry Bradley Smith.
Smith’s graduate student, Middleton Boon, synthesized a compound that moves certain phospholipid molecules from the outer edge of the cell membrane to the inner layer, causing the shape change. Building on that knowledge, Smith’s research group believes it understands how to move other phospholipids in the opposite direction, and that is the key to switching on the body’s natural mechanism for eliminating worn-out cells and perhaps cancer cells as well.
“When these molecules migrate to the outer layer of the cell membrane, they signal the body that the cell is old and should be cleared away,” explains Smith. Other structures called macrophages sense the signal and “vacuum up” the cell.
“We obviously have a very toxic substance here,” says Smith. “Therefore, to be usable, we have to find a way to target only cancer cells, perhaps by attaching the compound to an antibody that binds specifically with a specific type of tumor cell.” However, he cautions, that problem could take years to solve.
Smith’s lab chanced on the discovery while attempting to transport chloride ions across the cell membrane. The chemistry professor has been interested in chloride because abnormalities in chloride levels have been implicated in such diseases as muscular dystrophy and cystic fibrosis. Instead of moving chloride, they found their compound moved the phospholipid molecules. Unperturbed, they recognized the success of their “failure.”
“Serendipity plays a role in curiosity-driven research,” Smith notes. “But it very much is the phrase ‘Chance favors the prepared mind.’”
John Monczunski is an associate editor of this magazine.