Tag Archives: Dominic Lauzon

Researchers at University of Montéal decode how molecules “talk” to each

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An August 15, 2023 news item on ScienceDaily breaks news from the University of Montréal,

Two molecular languages at the origin of life have been successfully recreated and mathematically validated, thanks to pioneering work by Canadian scientists at Université de Montréal.

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Fascinating, non? An August 15, 2023 Université de Montréal news release (also on EurekAlert), which originated the news item, explaining how this leads to nanotechnology-enabled applications, Note: A link has been removed,

Published this week in the Journal of American Chemical Society, the breakthrough opens new doors for the development of nanotechnologies with applications ranging from biosensing, drug delivery and molecular imaging.

Living organisms are made up of billions of nanomachines and nanostructures that communicate to create higher-order entities able to do many essential things, such as moving, thinking, surviving and reproducing.

“The key to life’s emergence relies on the development of molecular languages – also called signalling mechanisms – which ensure that all molecules in living organisms are working together to achieve specific tasks,” said the study’s principal investigator, UdeM bioengineering professor Alexis Vallée-Bélisle.

In yeasts, for example, upon detecting and binding a mating pheromone, billions of molecules will communicate and coordinate their activities to initiate union, said Vallée-Bélisle, holder of a Canada Research Chair in Bioengineering 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 relies on our ability to understand and better employ molecular languages developed by living organisms,” he said.

Two types of languages

One well-known molecular language is allostery. The mechanism of this language is “lock-and-key”: a 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.

Although these two languages are observed in all molecular systems of all living organisms, it is only recently that scientists have started to understand their rules and principles – and so use these languages to design and program novel artificial nanotechnologies.

“Given the complexity of natural nanosystems, before now nobody was able to compare the basic rules, advantage or limitations of these two languages on the same system,” said Vallée-Bélisle.

To do so, his doctoral student Dominic Lauzon, first author of the study, had the idea of creating a DNA-based molecular system that could function using both languages. “DNA is like Lego bricks for nanoengineers,” said Lauzon. “It’s a remarkable molecule that offers simple, programmable and easy-to-use chemistry.”

Simple mathematical equations to detect antibodies

The researchers found that simple mathematical equations could well describe both languages, which unravelled the parameters and design rules to program the communication between molecules within a nanosystem.

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

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

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

In addition to expanding the synthetic toolbox to create the next generation of nanotechnology, the scientist’s discovery also shines a light on why some natural nanosystems may have selected one language over another to communicate chemical information.

Caption; The illustration depicts two chemical languages at the basis of 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 the activation by the key (pink). Credit: Monney Medical Media / Caitlin Monney

Here’s a link to and a citation for the paper,

Programing Chemical Communication: Allostery vs Multivalent Mechanism by Dominic Lauzon and Alexis Vallée-Bélisle. J. Am. Chem. Soc. 2023, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/jacs.3c04045 Online Publication Date: August 15, 2023 © 2023 American Chemical Society

This paper is behind a paywall.

Inspired by Picasso (or Schumpeter, Shiva, and others?), Université de Montréal researchers employ creative destruction to create new nanomachines

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I associate the idea of ‘creative destruction’ with economics and Joseph Schumpeter but it is more widespread and has a much longer history (see more at the end of this posting).

Here we have Université de Montréal researchers being inspired by the idea from (what was to me) an unexpected source, from a February 9, 2023 news item on Nanowerk,

“Every act of creation,” Picasso famously noted, “is first an act of destruction.”

Taking this concept literally, researchers in Canada have now discovered that “breaking” molecular nanomachines basic to life can create new ones that work even better.

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I love this image. Bravo!

Researchers Dominic Lauzon and Alexis Vallée-Bélisle Credit: Amélie Philibert & Benoit Gougeon | Université de Montréal

A February 9, 2023 Université de Montréal news release, which originated the news item, delves further into this act of creative destruction,

Evolved over millions of years

Life on Earth is made possible by tens of thousands of nanomachines that have evolved over millions of years. Often made of proteins or nucleic acids, they typically contain thousands of atoms and are less than 10,000 times the size of a human hair.

“These nanomachines control all molecular activities in our body, and problems with their regulation or structure are at the origin of most human diseases,” said the new study’s principal investigator Alexis Vallée-Bélisle, a chemistry professor at Université de Montréal.

Studying the way these nanomachines are built, Vallée-Bélisle, holder of the Canada Research Chair in Bioengineering and Bio-Nanotechnology, noticed that while some are made using a single component or part (often long biopolymers), others use several components that spontaneously assemble.

“Since most of my students spend their lives creating nanomachines, we started to wonder if it is more beneficial to create them using one or more self-assembling molecular components,” said Vallée-Bélisle.

A ‘destructive’ idea

To explore this question, his doctoral student Dominic Lauzon, had the “destructive” idea of breaking up some nanomachines to see if they could be reassembled. To do so, he made artificial DNA-based nanomachines that could be “destroyed” by breaking them up.

“DNA is a remarkable molecule that offers simple, programmable and easy-to-use chemistry,” said Lauzon, the study’s first author. “We believed that DNA-based nanomachines could help answer fundamental questions about the creation and evolution of natural and human-made nanomachines.”

Lauzon and Vallée-Bélisle spent years performing the experimental validations. They were able to demonstrate that nanomachines could easily withstand fragmentation, but more importantly, that such a destructive event allowed for the creation of various novel functionalities, including different sensitivity levels towards variation in component concentration, temperature and mutations.

What the researchers found is that these functionalities could arise simply by controlling the concentration of each individual component. For example, when cutting a nanomachine in three components, nanomachines were found to activate more sensitively at high concentration of components. In contrast, at low concentration of components, nanomachines could be programmed to activate or deactivate at specific moment in time or to simply inhibit their function.

“Overall, these novel functionalities were created  by simply cutting up, or destroying, the structure of an existing nanomachine,” said Lauzon. “These functionalities could drastically improve human-based nanotechnologies such as sensors, drug carriers and even molecular computers”.

Evolving new functionalities

Just as Picasso typically destroyed dozens of unfinished works to create his famous artworks, and just like muscles need to break down to get stronger, and innovative new companies are born by eliminating older competitors from the market, nanoscale machines can evolve new functionalities by being taken apart.

Unlike common machines like cell phones, televisions and cars, which are made by combining components using screws and bolts, glue, solder or electronics, “nanomachines rely on thousands of weak dynamic intermolecular forces that can spontaneously reform, enabling broken nanomachines to re-assemble,” said Vallée-Bélisle.

In addition to providing nanotechnology researchers with a simple design strategy to create the next generation of nanomachines, the UdeM team’s findings also shed light on how natural molecular nanomachines may have evolved.

“Biologists have recently discovered that about 20 per cent of biological nanomachines may have evolved through the fragmentation of their genes,” said Vallée-Bélisle. “With our results, biologists now have a rational basis for understanding how the fragmentation of these ancestral proteins could have created new molecular functionalities for life on Earth.”

Here’s a link to and a citation for the paper,

Functional advantages of building nanosystems using multiple molecular components by D. Lauzon & A. Vallée-Bélisle. Nature Chemistry volume 15, pages 458–467 (2023) DOI: https://doi.org/10.1038/s41557-022-01127-4 Published online: 09 February 2023 Issue Date: April 2023

This paper is behind a paywall.

Creative destruction

The Wikipedia entry for ‘Creative destruction’ is primarily on economic theory and various philosophies with no mention of Picasso. However, there is a fascinating segue into Eastern mysticism,

Other early usage

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Hugo Reinert has argued that Sombart’s formulation of the concept was influenced by Eastern mysticism, specifically the image of the Hindu god Shiva, who is presented in the paradoxical aspect of simultaneous destroyer and creator.

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On that note, have a lovely weekend.