Scientists develop DNA-based fluorescent nanoantenna to evaluate protein activity

Researchers at the Université de Montréal have developed a nanoantenna to track protein movements. The device offers a novel approach to track the structural changes of proteins over time, and it might help scientists better comprehend both natural and man-made nanotechnologies. The results were published in the Nature Methods journal.

Scientists develop DNA-based fluorescent nanoantenna to evaluate protein activity
Like a two-way radio that can both receive and transmit radio waves, the fluorescent nanoantenna designed by Alexis Vallée-Bélisle and his team receives light in one color and depending on the protein movement it senses, then transmits light back in another color, which we can detect. One of the main innovations of these nanoantennas is that the receiver part of the antenna (bright green) is also employed to sense the molecular surface of the protein studied via molecular interaction. Image Credit: Caitlin Monney.

The results are so exciting that we are currently working on setting up a start-up company to commercialize and make this nanoantenna available to most researchers and the pharmaceutical industry.”

Alexis Vallée-Bélisle, Study Senior Author and Professor, Chemistry, Université de Montréal

An antenna that works like a two-way radio

Scientists have created the first DNA synthesizer more than 40 years ago to generate molecules that encode genetic information. Alexis Vallée-Bélisle, who also holds the Canada Research Chair in Bioengineering and Bionanotechnology, says “in recent years, chemists have realized that DNA can also be employed to build a variety of nanostructures and nanomachines.

He further adds, “Inspired by the Lego-like properties of DNA, with building blocks that are typically 20,000 times smaller than a human hair, we have created a DNA-based fluorescent nanoantenna, that can help characterize the function of proteins.”

Like a two-way radio that can both receive and transmit radio waves, the fluorescent nanoantenna receives light in one color, or wavelength, and depending on the protein movement it senses, then transmits light back in another color, which we can detect,” stated Vallée-Bélisle.

The receiver section of the antenna is also used to detect the molecular surface of the protein investigated via molecular interaction, which is one of the major discoveries of these nanoantennae.

One of the main advantages of using DNA to engineer these nanoantennas is that DNA chemistry is relatively simple and programmable.”

Scott Harroun, Study First Author and Doctoral Student, Chemistry, Université de Montréal

Scott Harroun adds, “The DNA-based nanoantennas can be synthesized with different lengths and flexibilities to optimize their function. One can easily attach a fluorescent molecule to the DNA, and then attach this fluorescent nanoantenna to a biological nanomachine, such as an enzyme. By carefully tuning the nanoantenna design, we have created five nm long antenna that produces a distinct signal when the protein is performing its biological function.”

Scientists anticipate that fluorescent nanoantennas bring up plenty of new possibilities in biology and nanotechnology.

Harroun states, “For example, we were able to detect, in real time and for the first time, the function of the enzyme alkaline phosphatase with a variety of biological molecules and drugs. This enzyme has been implicated in many diseases, including various cancers and intestinal inflammation.”

In addition to helping us understand how natural nanomachines function or malfunction, consequently leading to disease, this new method can also help chemists identify promising new drugs as well as guide nanoengineers to develop improved nanomachines.”

Dominic Lauzon, Study Co-Author, Université de Montréal

Dominic Lauzon is doing his PhD in chemistry at UdeM.

According to the researchers, one of the key advantages of these nanoantennas is their ease of usage.

Perhaps what we are most excited by is the realization that many labs around the world, equipped with a conventional spectrofluorometer, could readily employ these nanoantennas to study their favorite protein, such as to identify new drugs or to develop new nanotechnologies,” concluded Vallée-Bélisle.

Source:
Journal reference:

Harroun, S. G., et al. (2021) Monitoring protein conformational changes using fluorescent nanoantennas. Nature Methods. doi.org/10.1038/s41592-021-01355-5.

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