MEASURING CELL FEVER SENSORS: Nanogel makes it possible
to sense tiny temperature differences inside cells
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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 Univer-
sity of Pavia, in GETTING WARM Water-rich interior of nanogel Italy, a specialist at low temperature quenches the fluorescence of in fluorescent water-sensitive fluorophores in cells (left). As temsensors, says this perature rises, the nanogel shrinks, water leaves, work “may open and the fluorophores shine more brightly (right). the way to establishing an experimental thermodynamics of cell processes.” Otto S. Wolfbeis of the University of Regensburg, in Germany, who also specialHeating izes in fluorescent sensors, Cooling says, “This is the first approach to high-resolution thermosensing inside cells.” Potential applications include seeing “whether cells are vital and = water ●,★ = fluorescent groups = ionic groups metabolically = cross-linker = thermosensitive polymer 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.—STU BORMAN
ECONOMY Chemtura struggles to stay whole during turbulent times Specialty chemical maker Chemtura is staring at about $375 million of debt that comes due in July. New CEO Craig A. Rogerson says the firm is now pursuing the sale of certain businesses to pay that looming debt. But he is also looking at other alternatives including negotiating an extension with bond holders, finding an infusion of money from an outside investor, and, as a last resort, declaring bankruptcy. “The primary avenue we are pursuing is the asset sale,” Rogerson, who replaced
former CEO Robert L. Wood in December, tells C&EN. The firm is targeting strategic rather than financial buyers. But with credit markets in disarray, there are no guarantees that a sale will take place, and so Chemtura is exploring all options. Like other chemical firms, Chemtura is reeling from the recession. Fourth-quarter sales dropped 23% to $690 million; sales for the year were off 5% to $3.5 billion. The company plans to release its earnings at the end of the month.
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However, Chemtura has been under duress for a long time. It put itself up for sale in December 2007 but didn’t find any takers. It suspended its dividend in November 2008. Shortly after Rogerson arrived, the firm said it would reduce costs by $50 million and slash 500 jobs. Rogerson, who successfully sold Hercules to Ashland last year, says he doesn’t plan to tidy up Chemtura for sale. He says he came to the company to lead its revival.—MARC REISCH
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