Dying cells dragged screaming under the microscope

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An eerie high-pitched song fills the air in a physics laboratory in Los Angeles. It is the scream of a yeast cell as it withers in a pool of alcohol, and it just may proclaim a useful new technique for cell biologists.

The master of this cellular torture chamber is physical chemist James Gimzewski of the University of California, Los Angeles. Best known for his work on manipulating single molecules during his career at IBM's Zurich research laboratory, Gimzewski has of late turned his nano-knowhow towards exploring single cells. He is trying to develop a new technique for studying the cell by listening to the sound that its membrane makes.

Gimzewski and graduate student Andrew Pelling have been looking closely at how the outer membranes of yeast cells vibrate, depending on the condition of the cells. Now they're teaming up with cancer pathologist Michael Teitell of the UCLA School of Medicine to establish whether this signature song could be used to monitor the health of a cell in response to both external stresses and internal ones, such as gene mutations.

To obtain such sensitive measures of the cell membrane, which moves only about two billionths of a metre with each vibration, Gimzewski and Pelling use the nanotechnologist's favourite tool — the atomic force microscope (AFM). The AFM's tip can be scanned over a surface to create a precise map of its topography. “We use the AFM as a type of stethoscope, to follow how cell membranes move,” says Gimzewski, who has christened the method 'sonocytology'.

The researchers find that strains of yeast emit slightly different sound patterns. When amplified, they sound a bit like rhythmic breathing. When researchers dribble some isopropyl alcohol onto one of the yeast cells, the pitch increases sharply, as if the cell is emitting a shrill cry. A dead cell produces the kind of static you might hear when tuning a radio.

Researchers have previously used an AFM to detect the pulsing surface of cardiac cells, which 'beat' even when removed from the body (S. G. Shroff, D. R. Saner and R. Lal, Am. J. Physiol. Cell Physiol. 269, C286–C292; 1995). But Gimzewski thinks that he's the first to listen to the membrane resonance of other cell types.

Gimzewski — a high-flyer at IBM who has published frequently in major scientific journals, including Nature — hasn't yet published anything on his idea. But he has discussed it with the LA Weekly, an alternative newspaper in Los Angeles, and he plans to demonstrate it this autumn at the Los Angeles County Museum of Art, in a nanotechnology exhibition held jointly with an artist with whom he has collaborated before, Victoria Vesna. He says that this approach fits in with his goal of taking science to a wider audience.

Sceptics point out that the technique may not work for mammalian cells, which have much softer membranes than yeast cells. But Jan Hoh, a physiologist at Johns Hopkins School of Medicine, says that he is intrigued by the concept of sonocytology. “If there are frequencies in the kilohertz range that truly are diagnostic to something going on in the cell, that would be interesting,” says Hoh. He cautions that treating cells with alcohol is too crude to reveal much, however.

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Zandonella, C. Dying cells dragged screaming under the microscope. Nature 423, 106–107 (2003). https://doi.org/10.1038/423106b

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