Building on previous research about the damage hydrogen peroxide can cause to cells and DNA, researchers at the Massachusetts Institute of Technology (MIT) have built a sensor array that, for the first time, can detect single molecules of hydrogen peroxide emanating from a single living cell. According to the researchers, the platform promises a new approach to understanding the signaling of reactive oxygen species at the cellular level, and in the context of this study, could lead to new targets for potential cancer drugs.
Publishing their findings in the March 7 online edition of Nature Nanotechnology, the chemical engineers say they have uncovered evidence that shows hydrogen peroxide appears to act as a signaling molecule in a critical cell pathway that stimulates growth. When that pathway goes awry, cells can become cancerous. This discovery could open the door for the development of new oncology drug targets, and to facilitate that possibility, the MIT team created a new sensor array made of carbon nanotubes to study the flux of hydrogen peroxide that occurs when a common growth factor called EGF activates its target, a receptor known as EGFR, located on cell surfaces.
Using the sensor, the team showed for the first time that hydrogen peroxide levels more than double when EGF activates EGFR, says lead researcher Michael Strano, a professor in MIT's chemical engineering department.
"What we did was use a nanosensor array that is the first ever constructed that can detect down to single molecules of hydrogen peroxide," Strano says. "I have been in the sensor field for a long time, and I feel like this is a triumph of nanotechnology. These are the most sensitive transducers to single molecules. You can't do any better than selectively detecting a single molecule."
Although it is still unclear exactly how hydrogen peroxide affects EGF, Strano says the team believes it may somehow amplify the EGFR signal, reinforcing the message to the cell. Because hydrogen peroxide is a small molecule that doesn't diffuse far (about 200 nanometers), the signal would be limited to the cell where it was produced.
The team also discovered that molecules of oxygen are consumed to generate the peroxide.
The researchers also found that in skin cancer cells, believed to have overactive EGFR activity, the hydrogen peroxide flux was 10 times greater than in normal cells. Because of that dramatic difference, Strano believes this technology could be useful in building diagnostic devices for some types of cancer.
"The take-home message of our study is that we built this nanosensor array that may be able to greatly inform the biochemistry of signaling," Strano says. "Now, with this array, we can measure it in real-time. It raises the prospect of having higher-precision tools to see signaling pathways that are otherwise difficult to detect. The list of biomolecules that we can now detect very specifically and selectively is growing rapidly."
Next, Strano's team will continue to study different forms of the EGF receptor to better characterize the hydrogen peroxide flux and its role in cell signaling, as well as work on carbon nanotube sensors for other molecules.
"We do have a patent on this concept, but we're also interested in developing this technique for commercial applications," he says. "These tools may be useful for drug discovery as well as fundamental science. Imagine, for example, if we made our sensor on the end of a fiber optic and could snuggle it up to tissue. We could probe it to see if it was expressing the EGFR pathway. Those are the directions we're moving in."
The study, "Detection of single-molecule H2O2 signaling from epidermal growth factor receptor using fluorescent single-walled carbon nanotubes," appeared in the March 7 online edition of Nature Nanotechnology. In addition to Strano, other authors on the study included Hong Jin, Daniel Heller, Marie Kalbacova, Jong-Ho Kim, Jingqing Zhang, Ardemis Boghossian and Narendra Maheshri.
Publishing their findings in the March 7 online edition of Nature Nanotechnology, the chemical engineers say they have uncovered evidence that shows hydrogen peroxide appears to act as a signaling molecule in a critical cell pathway that stimulates growth. When that pathway goes awry, cells can become cancerous. This discovery could open the door for the development of new oncology drug targets, and to facilitate that possibility, the MIT team created a new sensor array made of carbon nanotubes to study the flux of hydrogen peroxide that occurs when a common growth factor called EGF activates its target, a receptor known as EGFR, located on cell surfaces.
Using the sensor, the team showed for the first time that hydrogen peroxide levels more than double when EGF activates EGFR, says lead researcher Michael Strano, a professor in MIT's chemical engineering department.
"What we did was use a nanosensor array that is the first ever constructed that can detect down to single molecules of hydrogen peroxide," Strano says. "I have been in the sensor field for a long time, and I feel like this is a triumph of nanotechnology. These are the most sensitive transducers to single molecules. You can't do any better than selectively detecting a single molecule."
Although it is still unclear exactly how hydrogen peroxide affects EGF, Strano says the team believes it may somehow amplify the EGFR signal, reinforcing the message to the cell. Because hydrogen peroxide is a small molecule that doesn't diffuse far (about 200 nanometers), the signal would be limited to the cell where it was produced.
The team also discovered that molecules of oxygen are consumed to generate the peroxide.
The researchers also found that in skin cancer cells, believed to have overactive EGFR activity, the hydrogen peroxide flux was 10 times greater than in normal cells. Because of that dramatic difference, Strano believes this technology could be useful in building diagnostic devices for some types of cancer.
"The take-home message of our study is that we built this nanosensor array that may be able to greatly inform the biochemistry of signaling," Strano says. "Now, with this array, we can measure it in real-time. It raises the prospect of having higher-precision tools to see signaling pathways that are otherwise difficult to detect. The list of biomolecules that we can now detect very specifically and selectively is growing rapidly."
Next, Strano's team will continue to study different forms of the EGF receptor to better characterize the hydrogen peroxide flux and its role in cell signaling, as well as work on carbon nanotube sensors for other molecules.
"We do have a patent on this concept, but we're also interested in developing this technique for commercial applications," he says. "These tools may be useful for drug discovery as well as fundamental science. Imagine, for example, if we made our sensor on the end of a fiber optic and could snuggle it up to tissue. We could probe it to see if it was expressing the EGFR pathway. Those are the directions we're moving in."
The study, "Detection of single-molecule H2O2 signaling from epidermal growth factor receptor using fluorescent single-walled carbon nanotubes," appeared in the March 7 online edition of Nature Nanotechnology. In addition to Strano, other authors on the study included Hong Jin, Daniel Heller, Marie Kalbacova, Jong-Ho Kim, Jingqing Zhang, Ardemis Boghossian and Narendra Maheshri.
