Scientists at Université de Montréal (UdeM) have developed a nanoantenna to track the motions of proteins.
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 device is a new technique to track the structural variations of proteins over time – and may pave the way to helping researchers have a better insight into natural and human-designed nanotechnologies. Details of the device were recently reported in the journal Nature Methods.
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, Senior Study Author and Chemistry Professor, Université de Montréal
Works Like a Two-Way Radio
Over four decades, scientists invented the first DNA synthesizer to develop molecules that encrypt genetic data.
"In recent years, chemists have realized that DNA can also be employed to build a variety of nanostructures and nanomachines," said Vallée-Belisle, who also holds the Canada Research Chair in Bioengineering and Bionanotechnology.
"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," he said.
Like a two-way radio that can both receive and transmit radio waves, the fluorescent nanoantenna receives light in one colour, or wavelength, and depending on the protein movement it senses, then transmits light back in another colour, which we can detect. One of the main innovations of these nanoantennae is that the receiver part of the antenna is also employed to sense the molecular surface of the protein studied via molecular interaction.
Scott Harroun, Study First Author and Doctoral Student in Chemistry, Université de Montréal
“One of the main advantages of using DNA to engineer these nanoantennas is that DNA chemistry is relatively simple and programmable. 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,” Harroun added.
By carefully tuning the nanoantenna design, we have created five nanometer-long antenna that produces a distinct signal when the protein is performing its biological function.
Scott Harroun, Study First Author and Doctoral Student in Chemistry, Université de Montréal
Scientists are certain that fluorescent nanoantennas will open the door to many stimulating avenues in nanotechnology and biochemistry.
"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," said Harroun. "This enzyme has been implicated in many diseases, including various cancers and intestinal inflammation."
Added Dominic Lauzon, the study’s co-author doing his Ph.D. in chemistry at UdeM: "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."
One key progress facilitated by these nanoantennas is also their ease-of-use, the researchers stated.
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 favourite protein, such as to identify new drugs or to develop new nanotechnologies.
Alexis Vallée-Bélisle, Senior Study Author and Chemistry Professor, Université de Montréal
Journal Reference:
Harroun, S.G., et al. (2022) Monitoring protein conformational change using fluorescent nanoantennas. Nature Methods. doi.org/10.1038/s41592-021-01355-5.