DNA-based nanoantenna monitors the motions of proteins

Monday, 17 January, 2022

DNA-based nanoantenna monitors the motions of proteins

Researchers at Université de Montréal have created a nanoantenna to monitor the structural change of proteins over time, which could help scientists better understand natural and human-designed nanotechnologies. Their breakthrough has been described in the journal Nature Methods.

Over 40 years ago, researchers invented the first DNA synthesiser to create molecules that encode genetic information. In recent years, chemists have realised that DNA can also be employed to build a variety of nanostructures and nanomachines.

“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 characterise the function of proteins,” said Professor Alexis Vallée-Bélisle, senior author on the new study.

“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,” he explained. The receiver part of the antenna is also employed to sense the molecular surface of the protein studied via molecular interaction.

“One of the main advantages of using DNA to engineer these nanoantennas is that DNA chemistry is relatively simple and programmable,” said Scott Harroun, the study’s first author.

“The DNA-based nanoantennas can be synthesised with different lengths and flexibilities to optimise 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 nanometre-long antennae that produce a distinct signal when the protein is performing its biological function.”

Fluorescent nanoantennas open many exciting avenues in biochemistry and nanotechnology. “For example,” Harroun said, “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.”

Study co-author Dominic Lauzon added, “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.”

The nanoantennas are also easy to use, with Prof Vallée-Bélisle claiming 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”.

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

Image caption: 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.

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