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Volume 87 Issue 7 | p. 11 | News of The Week
Issue Date: February 16, 2009

Measuring Cell Fever

Nanogel makes it possible to sense tiny temperature differences inside cells
Department: Science & Technology
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Getting Warm
Water-rich interior of nanogel at low temperature quenches the fluorescence of water-sensitive fluorophores in cells (left). As temperature rises, the nanogel shrinks, water leaves, and the fluorophores shine more brightly (right).
Credit: Adapted from J. Am. Chem. Soc.
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Getting Warm
Water-rich interior of nanogel at low temperature quenches the fluorescence of water-sensitive fluorophores in cells (left). As temperature rises, the nanogel shrinks, water leaves, and the fluorophores shine more brightly (right).
Credit: Adapted from J. Am. Chem. Soc.

A NANOGEL-BASED MATERIAL that makes it possible to measure the temperature inside living cells at higher resolution than previously possible could facilitate studies of metabolism, cancer, and other temperature-dependent cellular phenomena.

Assistant professor of pharmaceutical sciences Seiichi Uchiyama of the University of Tokyo and coworkers developed the nanogel (J. Am. Chem. Soc., DOI: 10.1021/ja807714j). When introduced into cell cytoplasm, its fluorescence increases as the temperature goes up. These changes can be detected with a fluorescence microscope and used to measure temperature variations and absolute temperatures inside cells.

The technique's response time is in the millisecond range, and the resolution is as fine as 0.5 ºC—better by a factor of six to 10 than that of previous materials used to measure intracellular temperature. The earlier techniques, which used a europium complex or green fluorescent protein, haven't been practical because they not only have low resolution but are also prone to errors from pH and ionic strength changes. The new type of thermometer is not susceptible to these problems.

In the new nanogel, water-sensitive fluorescent groups and aggregation-preventing ionic groups are linked to a temperature-sensitive cross-linked polymer. When injected into low-temperature cells, the nanogel fills with water molecules, which quench the fluorescent groups' brightness. As temperature rises, the cross-linked polymer shrinks, squeezing out water molecules and permitting the fluorescent groups to shine more brightly.

Chemistry professor Luigi Fabbrizzi of the University of Pavia, in Italy, a specialist in fluorescent sensors, says this work "may open the way to establishing an experimental thermodynamics of cell processes."

Otto S. Wolfbeis of the University of Regensburg, in Germany, who also specializes in fluorescent sensors, says, "This is the first approach to high-resolution thermosensing inside cells."

Potential applications include seeing "whether cells are vital and metabolically active," Wolfbeis says. "Cancerous cells usually are warmer than noncancerous cells," he says, suggesting diagnostic uses as well. But it will be important to demonstrate that the nanogel is not toxic to cells, he notes.

The nanogel currently has to be injected into cells, but Uchiyama and coworkers hope to derivatize it with peptides that will permit spontaneous cell entry. It has a temperature range of 27–33 ºC at 0.5 ºC resolution or 26–36 ºC at 1 ºC resolution, but the range can be changed by using different temperature-sensitive polymers. "Although we did not describe it in the paper, we have some data on a thermometer having a different functional range," Uchiyama says.

 
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