By | August 5, 2023
Scientists have successfully recreated and mathematically validated two molecular languages ​​at the origin of life

Language at the basis of molecular communication

The illustration shows two chemical languages ​​that underlie molecular communication. The same white molecule, represented as a lock, is activated either via allostery (top) or multivalency (bottom). The allosteric activator (cyan) induces a conformational change of the lock while the multivalent activator provides the missing part of the lock, both enabling activation by the key (pink). Credit: Mooney Medical Media / Caitlin Mooney

Canadian researchers at University of Montreal have successfully recreated and mathematically confirmed two molecular languages ​​at the origin of life.

Their ground-breaking results, recently published in Journal of the American Chemical Societypaves the way for advances in nanotechnology, offering potential in areas such as biosensing, drug delivery, and molecular imaging.

Living organisms are made up of billions of nanomachines and nanostructures that communicate to create higher-order entities that can do many important things, such as move, think, survive, and reproduce.

“The key to the emergence of life is based on the development of molecular languages ​​- also called signaling mechanisms – which ensure that all molecules in living organisms work together to achieve specific tasks,” says the study’s principal investigator, UdeM biotechnology professor Alexis Vallée-Bélisle.

In yeast, for example, upon detection and binding of a mating pheromone, billions of molecules will communicate and coordinate their activities to initiate union, says Vallée-Bélisle, holder of a Canada Research Chair in Biotechnology and Bionanotechnology.

“As we enter the era of nanotechnology, many scientists believe that the key to designing and programming more complex and useful artificial nanosystems lies in our ability to understand and better use molecular languages ​​developed by living organisms,” he said.

Two types of language

A well-known molecular language is allostery. The mechanism of this language is “lock-and-key”: one molecule binds and modifies the structure of another molecule, directing it to trigger or inhibit an activity.

Another, lesser known molecular language is multivalency, also known as the chelate effect. It works like a puzzle: as one molecule binds to another, it facilitates (or not) the binding of a third molecule by simply increasing its binding interface.

Alexis Vallée Bélisle and Dominic Lauzon

Scientists Alexis Vallée-Bélisle (left) and Dominic Lauzon (right) are designing chemical languages ​​using DNA synthesis. Credit: Amélie Philibert | University of Montreal

Although these two languages ​​are observed in all molecular systems of all living organisms, it is only recently that scientists have begun to understand their rules and principles – and therefore use these languages ​​to design and program new artificial nanotechnology.

“Given the complexity of natural nanosystems, no one has previously been able to compare the fundamental rules, advantages or limitations of these two languages ​​on the same system,” said Vallée-Bélisle.

To do that, his graduate student Dominic Lauzon, first author of the study, had the idea to create one

DNA, or deoxyribonucleic acid, is a molecule made up of two long strands of nucleotides that wrap around each other to form a double helix. It is the genetic material in humans and almost all other organisms that carries the genetic instructions for development, function, growth and reproduction. Almost every cell in a person’s body has the same DNA. Most DNA is found in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).

” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”> DNA-based molecular system that could work with both languages. “DNA is like Lego bricks for nanoengineers,” Lauzon said. “It is a remarkable molecule that offers simple, programmable and easy-to-use chemistry.”

Simple mathematical equations for detecting antibodies

The researchers found that simple mathematical equations could well describe both languages, revealing the parameters and design rules for programming the communication between molecules within a nanosystem.

For example, while the multivalent language allowed control of both the sensitivity and cooperativity of the activation or deactivation of the molecules, the corresponding allosteric translation only allowed control of the sensitivity of the response.

With this new understanding at hand, the researchers used the language of multivalence to design and construct a programmable antibody sensor that allows the detection of antibodies over different concentration ranges.

“As demonstrated with the recent pandemic, our ability to precisely monitor the concentration of antibodies in the general population is a powerful tool for determining people’s individual and collective immunity,” says Vallée-Bélisle.

In addition to expanding the synthetic toolbox for creating next-generation nanotechnology, the researchers’ discovery also sheds light on why some natural nanosystems may have chosen one language over another to communicate chemical information.

Reference: “Programming Chemical Communication: Allostery vs Multivalent Mechanism” by Dominic Lauzon and Alexis Vallée-Bélisle, 15 Aug 2023, Journal of the American Chemical Society.
DOI: 10.1021/jacs.3c04045

Funding was provided by the National Sciences and Engineering Research Council of Canada, the Canada Research Chairs program and Les Fonds de recherche du Québec – Nature et technologies.

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