THE DEVICE: Commercially available quantum dots are nano-scale semiconductors that shift color in response to changes in temperature. The dots have two layers—an inner cadmium selenide core, and an outer zinc sulfide shell. Being biocompatible, researchers have used quantum dots as an alternative to fluorescent dyes to label and track cellular components, primarily in vitro.
Now, taking advantage of the tiny quantum dots' sensitivity to temperature, Haw Yang at Princeton University and his colleagues at the University of California, Berkeley, are repurposing them as an array of thermometers to use inside cells. They inserted the dots into mouse fibroblasts and measured temperature changes in various parts of the cell as they adjusted the temperature.
“We were asking whether the intracellular temperature response is homogeneous or not,” Yang told The Scientist.
WHAT'S NEW: The use of quantum dots as a nanothermometer is not new, but the application to cellular adaptations is. John Capobianco, the Concordia University Research Chair in Nanoscience, and colleagues published work last year showing that quantum dots could be used as a nanothermometer in HeLa cervical cancer cells. “It's nice that somebody has actually taken the idea of nanothermometers and used it to measure the temperature in a cell when you apply an external shock,” Capobianco said.
Yang's group added multiple quantum dots to each of 31 mouse fibroblasts. When sent into the cells, the dots landed up in different locations, providing a sampling of temperature responses throughout each cell. The researchers then added calcium, which is known to increase cellular temperature. As calcium entered the cells, the dots, for the most part, shifted toward the red light spectrum, indicating a temperature rise. But the researchers saw that the dots' response to the calcium was not uniform across the cell. Some dots indicated a rise as great as 8°C, whereas others showed little change at all.
The team also cooled down the cells from 37 to 15°C, and found similar results in 13 cells tested—some dots had a greater color shift than others, indicating that a cell's response to cold is also not uniform across the cell. “Different parts of the cell have different temperature responses,” Yang said, changing temperatures at different speeds and to different degrees. “That suggests to us that different parts of the cell generate heat to combat the cooling,” said Yang.
IMPORTANCE: The molecular mechanisms underlying the diverse temperature responses in a cell are the targets of Yang's upcoming work. He and his colleagues are investigating which proteins, enzymes and pathways might be responsible for the adaptations to heat and cold within the cell. Yang said he also believes that temperature could be a signaling mechanism for cells, and using quantum dots could reveal potential temperature pathways.
Nanothermometers have a potential role in cancer research and therapies too, said Kaushal Rege, a professor at Arizona State University who did not participate in this research. Hyperthermia is used as a method for killing tumors, and a thermometer could come in handy. “If these probes could be used to see how effective the treatment is, or to see what temperatures could be achieved in different parts of the cell and guide the treatment, that would be useful,” Rege said.
He added that nanothermometers could be employed to optimize the cryopreservation of tissues, by perhaps determining the most effective cooling protocols or monitoring how cells respond to different cooling techniques.
NEEDS IMPROVEMENT: In the current experiment, the researchers did not direct the location of the dots in the cell. The team could visualize the dots, but couldn't say whether they were near a mitochondrion or in the nucleus or on a membrane, for instance. Yang said he can envision methods that could allow researchers to target a dot to a certain point within the cell.
Rege agreed that it could be possible. In his own research he has found that closely related prostate cancer cell lines trafficked quantum dots to different parts of the cell. “If you can control the trafficking, you might get information on subcellular locations,” he told The Scientist.
Capobianco said that if quantum dots were to be applied in diagnostics or therapeutics, certain toxicity concerns will need to be addressed. Cadmium, which constitutes the core of some quantum dots, is a poison that can damage the liver, kidneys, bones and respiratory tract. Coating the dots might reduce their toxicity, but Capobianco said that additional studies would be required to confirm their safety before widespread clinical use.
J.-M. Yang, et al., “Quantum dot nano thermometers reveal heterogeneous local thermogenesis in living cells,” ACS Nano, doi:10.1021/nn201142f, 2011.