It’s like the world’s smallest game of “Operation.” A new set of nanotweezers can extract DNA and other single molecules from a living cell without killing it.
Examining the molecular contents of a single cell has traditionally required killing the cell by bursting it open. But that process provides only a single snapshot of the cell’s molecular makeup at the time of its death. The new nanotweezers, reported online December 3 in Nature Nanotechnology, could enable long-term analysis of what’s going on inside individual cells to better understand how healthy cells work and where diseased cells go wrong.
The nanotweezers comprise a glass rod with a tip less than 100 nanometers across, capped with two carbon-based electrodes. Applying an electric voltage to the tweezers creates a powerful electric field in the immediate vicinity of the electrodes, which can attract and trap biomolecules within about 300 nanometers of the tweezer tip.
Once caught in this 300-nanometer net, molecules are stuck until the tweezer voltage turns off. By positioning the needlelike tweezers with extreme precision, researchers can puncture specific cell compartments and fish for particular molecules.
Joshua Edel, a chemist at Imperial College London, and colleagues used their tweezers to extract DNA from the nuclei of human bone cancer cells without killing them. The researchers also plucked bits of protein-building instructions known as mRNA molecules out of the cytoplasm of artery cells.
Extracting mRNA from two different spots in a single cell, one hour apart, confirmed that the tweezers could be used to sample the same cell multiple times. In addition to nabbing individual molecules, the new nanotweezers lifted power-generating organelles called mitochondria out of nerve cells from mouse brains.
“So far, all our work has been done in petri dishes,” Edel says. The researchers plan to test their tweezers on cells inside tissue samples next.
“It is a very powerful technique, and opens new possibilities [for] molecular analysis inside a cell,” says Pak Kin Wong, a biomedical engineer at Penn State not involved in the work. Tweezing various proteins and other biomolecules from different parts of a cell over the course of its lifetime, for example, may provide new insight into how these molecules keep a cell up and running.
Extracting DNA from the nuclei of individual cells may also allow researchers to scan this genetic material for mutations that underpin diseases, Edel says. And monitoring cells’ molecular makeup could reveal how cells respond to new drugs.