Listening to Cells: Scientists probe human cells with high-frequency sound

Sound waves are widely used in medical imaging, such as when doctors take an ultrasound of a developing fetus. Now scientists have developed a way to use sound to probe tissue on a much tinier scale. Researchers from the University of Bordeaux in France deployed high-frequency sound waves to test the stiffness and viscosity of the nuclei of individual human cells. The scientists predict that the probe could eventually help answer questions such as how cells adhere to medical implants and why healthy cells turn cancerous.

“We have developed a new non-contact, non-invasive tool to measure the mechanical properties of cells at the sub-cell scale,” says Bertrand Audoin, a professor in the mechanics laboratory at the University of Bordeaux. “This can be useful to follow cell activity or identify cell disease.” The work will be presented at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa.

The technique that the research team used, called picosecond ultrasonics, was initially applied in the electronics industry in the mid-1980s as a way to measure the thickness of semiconductor chip layers. Audoin and his colleagues, in collaboration with a research group in biomaterials led by Marie-Christine Durrieu from the Institute of Chemistry & Biology of Membranes & Nano-objects at Bordeaux University, adapted picosecond ultrasonics to study living cells. They grew cells on a metal plate and then flashed the cell-metal interface with an ultra-short laser pulse to generate high-frequency sound waves. Another laser measured how the sound pulse propagated through the cells, giving the scientists clues about the mechanical properties of the individual cell components.

“The higher the frequency of sound you create, the smaller the wavelength, which means the smaller the objects you can probe” says Audoin. “We use gigahertz waves, so we can probe objects on the order of a hundred nanometers.” For comparison, a cell’s nucleus is about 10,000 nanometers wide.

The team faced challenges in applying picosecond ultrasonics to study biological systems. One challenge was the fluid-like material properties of the cell. “The light scattering process we use to detect the mechanical properties of the cell is much weaker than for solids,” says Audoin. “We had to improve the signal to noise ratio without using a high-powered laser that would damage the cell.” The team also faced the challenge of natural cell variation. “If you probe silicon, you do it once and it’s finished,” says Audoin. “If you probe the nucleus you have to do it hundreds of times and look at the statistics.”

The team developed methods to overcome these challenges by testing their techniques on polymer capsules and plant cells before moving on to human cells. In the coming years the team envisions studying cancer cells with sound. “A cancerous tissue is stiffer than a healthy tissue,” notes Audoin. “If you can measure the rigidity of the cells while you provide different drugs, you can test if you are able to stop the cancer at the cell scale.”

(Photo: Image courtesy of UCSD Jacobs)

Can You Smell Yourself?

You might not be able to pick your fingerprint out of an inky lineup, but your brain knows what you smell like. For the first time, scientists have shown that people recognize their own scent based on their particular combination of major histocompatibility complex (MHC) proteins, molecules similar to those used by animals to choose their mates. The discovery suggests that humans can also exploit the molecules to differentiate between people.

"This is definitely new and exciting," says Frank Zufall, a neurobiologist at Saarland University’s School of Medicine in Homburg, Germany, who was not involved in the work. "This type of experiment had never been done on humans before."

MHC peptides are found on the surface of almost all cells in the human body, helping inform the immune system that the cells are ours. Because a given combination of MHC peptides—called an MHC type—is unique to a person, they can help the body recognize invading pathogens and foreign cells. Over the past 2 decades, scientists have discovered that the molecules also foster communication between animals, including mice and fish. Stickleback fish, for example, choose mates with different MHC types than their own. Then, in 1995, researchers conducted the now famous “sweaty T-shirt study,” which concluded that women prefer the smell of men who have different MHC genes than themselves. But no studies had shown a clear-cut physiological response to MHC proteins.

In the new work, Thomas Boehm, a biologist at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany, and colleagues first tested whether women can recognize lab-made MHC proteins resembling their own. After showering, 22 women applied two different solutions to their armpits and decided which odor they liked better. The experiment was repeated two to six times for each participant. Women preferred to wear a synthetic scent containing their own MHC proteins, but only if they were nonsmokers and didn’t have a cold. The study did not determine which scents women preferred on other people, but past studies on perfume have shown that individuals prefer different smells on themselves than on others.

The researchers wanted to know whether the preferences were truly rooted in the brain’s response to the proteins. So next, they used functional magnetic resonance imaging to measure changes in the brains of 19 different women when they smelled the various solutions, in aerosol form puffed toward their noses. “Sure enough, there again was a clear difference between the response to self and non-self peptides,” Boehm says. “There was a particular region of the brain that was only activated by peptides resembling a person’s own MHC molecules.” The brain had a similar response to all non-self MHC combinations, suggesting that any preference for how other people smell is a preference for non-self, not for particular MHC types.

(Image: Getty)