Engineered cardiac cells flash when they beat
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SAN FRANCISCO — A protein borrowed from Dead Sea microbes and re-engineered by researchers makes heart cells light up with every contraction. The flashing cells may offer a way to predict whether new drugs will cause heart problems in people, Harvard researchers reported December 17 at the American Society for Cell Biology annual meeting.
Adam Cohen and his colleagues took a protein that helps a Dead Sea microorganism harvest energy from sunlight and broke the molecule so it works only in reverse, giving off instead of absorbing light under certain conditions. When placed in heart cells, the protein — called archaerhodopsin 3, or Arch for short — flashes dim red light when heart cells get an electrical signal to beat, Cohen reported. A different version of the Arch protein blinks blue when calcium enters the cell or is released from storage depots inside the cell to trigger heart muscle contractions. (Click here to view a movie of the protein in action.)
The idea for the flashing cells came from a new field of research known as optogenetics, in which researchers use flashes of light to control the activity of nerve cells. The new technique doesn’t alter the way the heart cells function; it simply allows Cohen and his colleagues to monitor the beating of human heart cells.
The researchers placed the red and blue twinkling proteins into human skin cells that had been reprogrammed to make stem cells and then were coaxed into becoming heart muscle cells. Even growing in a laboratory dish, the cells beat in time with each other. In the future, reprogrammed cells could be created from skin cells taken from people with genetic heart problems to learn more about how their condition affects heart cell function.
Splashing drugs that affect heart rate on the cells changes the way the cells beat and alters the pattern of flashes from the monitoring proteins. Cohen envisions using his flashy cells to screen out drugs that could cause heart problems before they go into clinical trials. People might one day be able to have some of their own skin cells made into dishes of heart cells to test how they might respond to certain drugs.
The researchers also engineered the monitoring proteins into the hearts of zebra fish, which are partially transparent, allowing Cohen and his team to see how the heart cells work in an actual organism and not just in a lab dish. Drugs can be added to the water the fish swim in to test for any toxic effects on the heart.
Putting the proteins into zebra fish is a good way to see how cells work together in a tissue, said Simon Atkinson, a cell biologist at the Indiana University School of Medicine in Indianapolis. The researchers may need to tinker with the proteins to make them brighter for studying hearts in mice, rats or other nontransparent lab animals, he said.
An engineered heart cell flashes blue (top) to reveal the concentration of calcium in the cell. A different view of the same cell (bottom) indicates when the cell receives an electrical signal to beat.
Credit: A. Cohen/Harvard Univ.
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