Decoding how molecules 'talk' to each other to develop new nanotechnologies

Pioneering study by Canadian scientists at Université de Montréal has successfully reproduced and mathematically confirmed two molecular languages at the genesis of life.

The research "Programming chemical communication: allostery vs. multivalent mechanism," which was published on August 15, 2023 in the Journal of the American Chemical Society, provides up new avenues for the advancement of nanotechnologies with uses in biosensing, drug delivery, and molecular imaging.

The billions of nanomachines and nanostructures that make up living things communicate with one another to form higher-order entities that are capable of performing numerous critical tasks, including moving, thinking, surviving, and procreating.

According to Alexis Vallée-Bélisle, a professor of bioengineering at the University of Minnesota, "the development of molecular languages, also known as signaling mechanisms, which ensure that all molecules in living organisms are working together to achieve specific tasks, is the key to life's emergence."

According to Vallée-Bélisle, who holds a Canada Research Chair in Bioengineering and Bionanotechnology, billions of molecules in yeasts, for instance, communicate and coordinate their actions to begin union when they detect and bind a mating pheromone.

As we go into the age of nanotechnology, he continued, "many scientists believe that the key to designing and programming more sophisticated and practical artificial nanosystems depends on our capacity to understand and better utilize molecular languages developed by living organisms."

two different language groups

Allostery is one well-known molecular dialect. A molecule connects to another molecule and changes its structure, causing it to be directed to either activate or inhibit an action. This is the "lock-and-key" mechanism of this language.

Multivalency, commonly referred to as the chelate effect, is a different, less well-known molecular language. It functions like a puzzle: when molecules attach to one another, the binding of a third molecule is either made easier or harder by simply expanding the binding interface of the first molecule.

Although these two languages are present in all molecular systems of all living things, scientists have only lately begun to grasp their fundamental principles. As a result, they may now be used to construct and program cutting-edge artificial nanotechnologies.

Given the complexity of natural nanosystems, Vallée-Bélisle said that no one has ever been able to compare the fundamental principles, benefits, or drawbacks of these two languages on the same system.

In order to do this, Dominic Lauzon, his PhD student and the study's lead author, came up with the concept of building a DNA-based molecular system that could communicate using both languages. For nanoengineers, DNA is similar to Lego blocks, according to Lauzon. It's a fantastic molecule that offers straightforward, programmable chemistry that is simple to employ.

simple mathematical formulas for antibody detection

The researchers deciphered the parameters and design criteria to program the communication between molecules within a nanosystem and discovered that straightforward mathematical equations could effectively explain both languages.

For instance, while the comparable allosteric translation only allowed control of the response's sensitivity, the multivalent language allowed control of both the sensitivity and cooperativity of the molecules' activation or deactivation.

With this new knowledge at their disposal, the researchers designed and engineered a programmable antibody sensor that enables the detection of antibodies over a variety of concentrations using the language of multivalency.

According to Vallée-Bélisle, "as demonstrated by the recent pandemic, our ability to precisely monitor the concentration of antibodies in the general population is a powerful tool to assess the people's individual and collective immunity."

The scientist's research illuminates why certain natural nanosystems may have chosen one language over another to exchange chemical information in addition to broadening the synthetic toolkit to produce the next generation of nanotechnology.