Taking a person’s temperature is no sweat: slip a thermometer under their tongue, say, and watch the reading climb to somewhere in the vicinity of 98 degrees Fahrenheit. But that single number actually results from each of the 30 trillion or so cells in the human body generating its own heat. The dispersal of that heat sets an overall body temperature, with different types of cells contributing to varying degrees.
To really understand how living things regulate their body’s temperature, researchers must look to individual cells. But even as scientists’ abilities to spy on molecular interactions up close have improved tremendously over the past decade, they have struggled to develop tools that accurately measure a cell’s thermal properties from the inside.
Now a new study fills in a crucial knowledge gap. For the first time, researchers have measured the thermal conductivity—the rate at which heat is conducted—inside human cells. In a paper published on Friday in Science Advances, scientists used miniscule diamond-based sensors that simultaneously release and measure heat to demonstrate that heat dissipates in cells much more slowly than they previously believed. “That was very surprising for us and others in the field,” says Madoka Suzuki, a biophysicist at Osaka University in Japan and a co-author of the paper. Because the fluid in cells is water-based, scientists have generally assumed it carries heat much like water does. Instead heat dissipates in cells about five times more slowly—a speed more akin to the way it dissipates in oil. Until now “nobody knew this basic property of living cells,” Suzuki says. “Without that value, we cannot model how cellular temperature changes.”
“These are intriguing results that need to be better understood,” says Harvard University physicist Mikhail Lukin, who has developed sensors for probing temperatures within cells but did not work on this project. “If they hold, they would be quite important.”
The findings may help resolve a major mystery about cell temperatures that has flummoxed biologists: the existence of hyperlocalized heat spikes. Scientists have reported transient differences of a few degrees F from spot to spot within a cell, a space that ranges from about five to 120 microns in diameter in humans. (That is somewhere between the width of a clump of dust mite poop and that of an actual dust mite.) One 2018 study even claimed that mitochondria, cells’ pill-shaped energy pumps, run at a toasty 122 degrees F.
The idea that cells can harbor such large temperature gradients is surprising because in such a minute space, a sharp rise in heat should dissipate quite quickly. But the reports have been convincing, says Luís Carlos, a nanoscientist at the University of Aveiro in Portugal, who studies intracellular thermometry but was not involved in the new study. “I think experimental results in the last five years consistently point out the existence of temperature fluctuations inside the cell.”
In the new work, Suzuki and his colleagues built on technology first developed by Lukin to create a fluorescent nanodiamond sensor coated in a heat-releasing polymer. Local temperature changes ever so slightly expand imperfections in the nanodiamond, changing the degree to which it fluoresces when hit by a laser. Because diamonds are so inert, the method is much more stable than other types of probes, Lukin says.
The heat conductivity identified in the new work can explain smaller heat spikes of a couple of degrees F, though not the massive heat surge in mitochondria, Suzuki says. He speculates that they may act as a previously unrecognized signaling system within the cell. For example, a boost in heat might tell proteins to fold or unfold, drive certain enzymatic reactions or provide feedback to channels that regulate calcium levels in muscles.
Suzuki and Lukin agree that it will still take more research to pin down whether these gradients really exist and, if so, how they are generated. “There is this outstanding problem that people are very confused about, and it has to be resolved,” Lukin says. “The fact that this new tool can answer this biological question—I think that’s really new.”