Ruthenium compound can detect signs of stressed-out cells

Carbon monoxide can be a toxic gas, but it’s also an important messenger inside cells, possibly playing a role in signaling involved in inflammation and cardiovascular disease. Increasing CO levels basically can serve as a warning sign that cells are in trouble. Changes in CO are also linked to the viscosity of the cell’s contents because cells under stress produce reactive oxygen species (ROS) and spur CO-producing enzymes into action. Both these changes increase cell viscosity.

Now researchers report a molecular probe that can simultaneously measure changes to CO levels and the gloopiness of a cell’s interior (Angew. Chem. 2020, DOI: 10.1002/anie.202008224). A sensor that can take both measurements at the same time is unprecedented, the team says, and they hope it could speed up and simplify diagnoses of some diseases.

James Wilton-Ely of Imperial College London and his colleagues’ ruthenium probe reacts instantaneously with CO, triggering an attached fluorescent dye to glow. Researchers can then measure cell viscosity by monitoring how that glow decays over time. Fluorescence decay depends on how freely the dye can rotate in a solution, with a sluggish decay indicating that the molecule is spinning slowly in a viscous environment.

The researchers first tested the new sensor in cells starved of oxygen, which triggers the release of CO, and the spike in CO levels was detected by the fluorescence microscope. They also introduced CO into cells in two different ways and detected changes in the cells’ viscosities.

There are palladium-based sensors that already can detect CO, and Wilton-Ely’s system doesn’t match those for sensitivity. But the new compound has multiple advantages, he says. The palladium salts are toxic, and the carbonylation reaction required to get them to fluoresce takes a long time—typically over 40 min. The ruthenium sensor is nontoxic and its fluorescence switches on immediately.

The utility of the system could be in a cheap and accessible test to determine whether cells are stressed and require further investigation, or not. “At the moment we are not able to use it as an indicator of a certain pathology,” Wilton-Ely says. But the team is working with immuno-oncologists to see if they can use the sensor to study cell samples from breast cancer patients undergoing chemotherapy.

This new approach to CO detection is “a truly important contribution to the field,” says Brian Michel at the University of Denver, who also works on CO detection. He suggests that the system might be useful for differentiating how cells respond to CO produced inside the cell versus CO-releasing molecules added to the cell, which researchers are studying in hopes of determining whether CO could be used therapeutically.