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New technology reveals changes within individual living cells

Researchers at Columbia University have developed a remarkable new tool that can closely examine changes within living cells. The technology may ultimately provide a more precise way to remove tumors, or could lead to an easier method of detecting head injuries and developmental disorders.

“We can use this technology to visualize metabolic activities in a wide range of animals,” said senior author Professor Wei Min. “By tracking where and when new proteins, lipids and DNA molecules are made, we can learn more about how animals develop and age, and what goes wrong in the case of injury and disease.”

The tool combines the use of heavy water (D2O) as a chemical tracer with an advanced laser-imaging method called stimulated Raman scattering (SRS). Heavy water is incorporated into newly-made proteins once it is metabolized by cells, and the deuterium forms chemical bonds with carbon.

The team discovered that these carbon-deuterium bonds vibrate at different frequencies when the light hits them, which allows each macromolecule to be identified. The experts found that they can track the growth of new proteins, lipids, and DNA in organs based on these unique frequency signatures.

In other words, the new method makes it possible to observe subcellular changes in real time.

“We get a continuous picture of what’s happening inside living animal cells. Previously, we had only a snapshot,” said study co-lead author Lingyan Shi, a postdoctoral researcher at Columbia.

To test the technology, the researchers diluted regular water with D2O and fed it to roundworms, mice, and zebrafish embryos. Over the course of hours and days, the team observed the buildup of new proteins, lipids, and DNA in a variety of tissues using the SRS laser.

In one experiment, the experts were able to witness a bright line that appeared around fast-growing brain and colon tumors in mice. As the cancerous cells divided, more deuterium was incorporated into their newly-made proteins and lipids.

“This method creates a sharp line between healthy and cancerous tissue, making it much easier to remove the tumor,” said Shi.

The research has also provided new insight into cell development and aging. For example, the scientists watched fat production rise and fall in the roundworm’s reproductive system as it aged. Clumps of new protein could be seen forming in the older worm’s body, suggesting that deuterium-labeled SRS imaging could be used to track age-related disease.

Image Credit: Min lab/Columbia

Through various other trials, the experts found that the technology could also be used to determine whether a child’s brain is developing properly, or if a patient is suffering from multiple sclerosis.

Eric Potma is a Chemistry professor at the University of California at Irvine who was not involved in the study.

“The beauty of this mapping method is its simplicity,” said Professor Potma. “It produces vivid images of metabolic activity in tissues with seemingly minimal effort. As the SRS microscope continues to get smaller, deuterium-labeled SRS imaging may help to catch tumors at much earlier stages.”

The study is published in the journal Nature Communications.

By Chrissy Sexton, Staff Writer

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