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Single Molecule Research

By Marlene Cimons, National Science Foundation

Everything is composed of molecules, including human cells and non-living materials. Not surprisingly, if scientists want to better understand the action of cells or how chemical reactions can create compounds, it helps to know more about how single molecules behave.   

Until recent years, however, it hasn’t been easy to study individual molecules, nor has it always been accurate. For example, there typically are only a few molecules of any one kind per cell, so it was difficult in the past for researchers to see them unless they added massive amounts of additional molecules. This, however, risked changing the cells’ behavior, and possibly distorting the results.

During the 1990s, however, it became possible to detect a single molecule with the introduction of highly sensitive fluorescence microscopy that enabled researchers to see single molecules in their natural environments, and in their normal amounts--in other words, in the real world, not an artificially skewed one. These instruments consistently have improved over the years, and promise to help answer important questions in biology, medicine and nanotechnology.

“Single-molecule microscopy has evolved into the ultimate-sensitivity toolkit to study systems from small molecules to living cells,” says Nils Walter, a University of Michigan chemistry professor. “It raises the prospect of revolutionizing the modern biosciences.”

Single-molecule science potentially could inspire new approaches to cancer detection and treatment, as well as that of other diseases, and have a major impact on technology by providing efficient, economical and environmentally-friendly ways to manufacture a variety of products.   

Walter directs the Single Molecule Analysis in Real Time (SMART) Center, a new facility at the University of Michigan that hopes to bring together basic scientists, engineers and clinical researchers to further expand the growing field of single molecule science.

While single-molecule science is not new, its equipment generally has not been widely accessible to scientists. The center, which opened in April, intends to make its equipment and expertise available “to anyone with an idea, a scientific system, a catalyst they want to test, or a molecule they want to see,” Walter says. “This makes it broadly usable to more people, not just to the pioneers in the field.”

The idea to establish the center grew out of a 2006 conference at the university convened to discuss the future of single molecule science. Most of the participants, which included many scientists already deeply involved in this type of research, concluded that the discipline “was missing a basic education mission, opportunities for people who have biological materials of different kinds to become educated in what these tools do, and how to use them to see things they never could see before,” Walter says.

The National Science Foundation is supporting the center with nearly $1.2 million over three years, as part of the American Recovery and Reinvestment Act of 2009.  In addition to purchasing the instruments, the effort has created a number of new jobs both at the university and within the companies that manufacture the sophisticated instruments.

The latest technology “brings the molecules as close to reality as possible,” Walter says. In cancer, for example, “now we can look at a cell in a much less perturbed way, in a much more natural biological context. We can now learn how a cell becomes a cancer cell. If you compare the cancer molecules to normal individual cell molecules, you can better understand what makes them cancerous, and do a better job of targeting them for therapy,” he says.

“We can localize the molecules within the cell, with better resolution, and watch them go about their business,” Walter adds.  “This is the promise of single-molecule tools - to see how a cell becomes cancerous, to see how the molecules are altered, to follow the molecules in the cell and see how they go about transforming the cell into a cancer cell.”