New imaging technology could reveal cellular secrets

Georgia Tech researchers have combined two biological imaging technologies (AFM and NMR) to learn how good cells go bad
April 29, 2013

This image illustrates the concept for a new type of technology that combines two biological imaging methods — atomic force microscopy and nuclear magnetic resonance — to create a new way to study cancer-cell metastasis and other disease-related processes (credit: Xin Xu/Purdue University)

What causes a cell to metastasize into a cancerous tumor? To find out, Corey Neu, an assistant professor in Purdue University‘s Weldon School of Biomedical Engineering, and colleagues have combined an atomic force microscope (AFM) and a nuclear magnetic resonance system.

An AFM uses a tiny vibrating probe called a cantilever with a tip that travels over the surface of a cell to yield information about materials and surfaces at the scale of nanometers, or billionths of a meter.

Because the instrument enables scientists to “see” objects far smaller than possible using light microscopes, it could be ideal for studying molecules, cell membranes, and other biological structures.

However, the AFM doesn’t provide information about the biological and chemical properties of cells. So the researchers added a nuclear magnetic resonance detector, using a metal microcoil on the AFM cantilever. An electrical current is passed though the coil, causing it to exchange electromagnetic radiation with protons in molecules within the cell and inducing another current in the coil, which is then detected.

“You could detect many different types of chemical elements, but in this case hydrogen is nice to detect because it’s abundant,” Neu said. “You could detect carbon, nitrogen and other elements to get more detailed information about specific biochemistry inside a cell.” The NMR function can also be added to commercially available AFM probes with
minor modiļ¬cations.

Such an advance makes it possible to perform “mechanobiology” studies to learn how forces exerted on cells influence their behavior. In work focusing on osteoarthritis, their research includes the study of cartilage cells from the knee to learn how they interact with the complex matrix of structures and biochemistry between cells.simultaneously study the mechanical and biochemical behavior of cells, which could provide new insights into disease processes.

Being able to study a cell’s internal workings in fine detail would likely yield insights into the physical and biochemical responses to its environment. The technology could help researchers study individual cancer cells, for example, to uncover mechanisms leading up to cancer metastasis for research and diagnostics.

Future research might include studying cells in “microfluidic chambers” to test how they respond to specific drugs and environmental changes.

A U.S. patent application has been filed for the concept. The research has been funded by Purdue’s Showalter Trust Fund and the National Institutes of Health.