Moving DNA Molecules With Magnetic Tweezers

January 10, 1997

Denis Wirtz switches on his magnetic tweezers, grabs hold of a single DNA molecule and uses a joystick to steer it carefully through a solution. Wirtz, an assistant professor of chemical engineering at The Johns Hopkins University, is not playing an electronic game. He is manipulating molecules in ground-breaking research that could lead to new surgical tools and drug delivery systems. Using Wirtz's device, a physician may soon magnetically move a microscopic sac filled with cancer-killing medicine through a patient's veins, then empty it directly into diseased cells.

"You could use these magnetic tweezers to transport a vesicle or fluid-filled cell containing a drug," Wirtz explains. "You could use the tweezers as sort of a surgical tool to take it to the targeted area and then penetrate the diseased cells. It could be done very easily. Right now, you can move things inside a vein mechanically, but it's very invasive. With magnetic force, it's non-invasive."

Wirtz, who invented the device three years ago as a postdoctoral student in Europe, is reconstructing it in a new lab at Hopkins. Here, he hopes to turn the magnetic surgery idea into reality. He has attracted more than $500,000 in federal and private grants to continue studying and refining the tool.

The forces that allow Wirtz's device to work are already familiar to any child who has played with a magnet. If you place a sheet of paper over a steel button, then hold the magnet on top of the paper, you can move the button without touching it. Wirtz's magnets are three sets of coiled copper wire, each connected to a power source. The coils are positioned to produce electromagnetic fields in three dimensions: backward and forward, side to side, and up and down. With a joystick, Wirtz can shift the amount of electricity flowing to each set of coils. That lets him move a magnetic object in any direction. In his Hopkins lab, Wirtz has reconstructed his device to move molecules back and forth beneath a microscope in one dimension. He plans to add more magnets and a joystick to recreate the three-dimensional movement.

A DNA molecule, by itself, is not magnetic. Wirtz overcomes this hurdle with iron oxide beads, each no larger than one-hundredth of a micron in diameter. (A micron is one-thousandth of a millimeter.) He coats these magnetic beads with a protein called biotin. Within a solution, biotin automatically attaches itself to an end of a DNA molecule, giving it a tiny magnetic partner. When he switches on his electromagnets, Wirtz can then move the DNA molecules. By coating the beads and the DNA with fluorescent dye, he can observe their activity through a microscope.

This breakthrough has allowed Wirtz to make critical measurements of how a single DNA molecule moves and changes shape. At rest, DNA is a long, chain-like molecule that coils itself into the shape of a ball. When one end is pulled by a magnet, the molecule stretches into a narrow trumpet-like shape. Wirtz used the magnetic tweezers in his home city of Brussels, Belgium, to become the first scientist to measure the friction coefficient-- force divided by velocity--of a single DNA molecule. In 1995, his findings were published in Physical Review Letters. He joined the faculty of Hopkins' Whiting School of Engineering two years ago.

For his research, Wirtz selected the lambda-phage DNA molecule, found in a virus, because, at 17 microns from end to end, it is large enough to view with a simple benchtop microscope. But he believes the magnetic manipulation technique will work with other biological polymers, including those designed to carry medicine to a specific site. The magnetic tweezers could also be used in genetic engineering, where scientists need to move genes and enzymes within microscopic cells, Wirtz says. At Hopkins, he is able to advance his research with the aid of a costly confocal microscope, which provides far enhanced resolution. By connecting camera equipment to the microscope, Wirtz has been able to collect video and computer images of DNA molecules in motion. This has allowed him to begin testing theories developed over the past 30 years. "You see this DNA moving around, and it's something that people had only imagined but had never seen," Wirtz says. "This is exciting stuff!"
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Johns Hopkins University

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