All living cells generate nanoscale vibrations that can be used in research and diagnostic settings to monitor the cells’ responses to external stimuli, particularly antibiotics and other pharmaceuticals. The origins of the vibrations, however, are not fully understood. Several hypotheses are on the table, including motion of organelles, action of ion pumps, redistribution of cellular material, conformational changes in proteins, and flagellar motion.

Researchers have developed a suite of tools to meet the challenge of noninvasively probing cell biomechanics. Cantilevers like those used in atomic force microscopy have become particularly popular for bacterial cell populations- The cells stick to the probe, and they bend the cantilever with their motion. But that technique requires hundreds or even thousands of cells to generate enough vibrations to overcome environmental noise. High-resolution fluorescence microscopy probes individual cells, but it requires cell labeling that may not be feasible in clinical settings.

A new graphene-based device developed by Irek Rosłoń, Aleksandre Japaridze, and coworkers at Delft University of Technology in the Netherlands is sensitive enough to detect nanoscale oscillations from a single cell in its natural state. The density of the nanomotion sensors can reach more than 10 000 per square millimeter, which makes it ideal for high-throughput screening.

Each sensor consists of a graphene drum—an 8-µm-diameter disk of bilayer graphene suspended above a 285-nm-deep well etched in silica. A scanning electron microscope image of a sensor with a single Escherichia coli bacterium sitting on it is shown in the first figure. The drum owes its motion sensitivity to its low mass and high stiffness. As a bacterium wiggles on the drumhead, it causes deflections of up to 60 nm that can be measured using laser interferometry.

To quantify the effect of flagella on the cells’ motion, the researchers compared the vibrations of four genetically modified E. coli strains- a hypermotile one with extra flagella compared with the wild type, a minimally motile one that lacks an essential element for flagellum synthesis, a nonmotile one with disabled flagellar motors, and a flagellaless one with functioning motors. The probability distributions of membrane displacements, shown in the left graph in the figure below, indicate that flagellar motion is the primary source of activity; when the flagella are disabled, the motion disappears almost entirely.

The researchers also studied the influence of ion pumps on cellular motion by administering the drug cadaverine, which blocks ion transport through the cell’s membrane. The right graph in the figure below shows a reduction in motility, but the change is small compared with that caused by changes to the flagella. Administering the antibiotic A22, which affects cell-wall synthesis and causes the cells to become rounder, had no effect on the cells’ motion.

Arrays of graphene nanodrums could be used to track a cell’s time-dependent response to a stimulus or identify individual antibiotic-resistant bacteria in a population. The devices could potentially be integrated into rapid-screening tests for the development of drugs or personalized medical treatments. (I. Rosłoń et al., Nat. Nanotechnol., 2022, doi-10.1038/s41565-022-01111-6.)