Making a tiny robot out of DNA to explore cell processes that are undetectable to the human eye… You could be excused for thinking it is science fiction, but it is actually the focus of significant research being conducted at the Structural Biology Center in Montpellier by researchers from Inserm, CNRS, and Université de Montpellier. This extremely cutting-edge “nano-robot” could make it possible to analyze mechanical forces at microscopic scales in greater detail, which are important for many biological and pathological processes. A recent study that was published in Nature Communications details it.
When micromechanical forces act on our cells, they send out biological signals that are important for many cell processes that either cause diseases or keep our bodies running normally.
For instance, the sensation of touch depends in part on the application of mechanical forces to particular cell receptors (the discovery of which was this year rewarded by the Nobel Prize in Physiology or Medicine). These touch-sensitive sensors, or mechanoreceptors, also enable the control of other important biological processes, including blood vessel constriction, pain perception, breathing, or even the detection of sound waves in the ear, among others.
Many disorders, including cancer, are characterized by the malfunctioning of this cellular mechanosensitivity. Cancer cells move throughout the body by vibrating and constantly adjusting to the mechanical characteristics of their microenvironment. Only because mechanoreceptors can pick up on specific forces and send that information to the cytoskeleton can cells change in this way.
We now know relatively little about the molecular processes underlying cell mechanosensitivity. A number of technologies are already available to apply regulated forces and research into these systems, although they have several drawbacks. Because we can’t look at more than one cell receptors at a time, using them to get a lot of information is very expensive and takes a lot of time.
Origami DNA structures
The research group at the Structural Biology Center (Inserm/CNRS/Université de Montpellier), led by Inserm researcher Gatan Bellot, chose to apply the DNA origami technique to present a substitute. This makes it possible for DNA molecules to serve as the building blocks for 3D nanostructures that self-assemble into a predetermined shape. In the last ten years, nanotechnology has made a lot of progress because of this method.
As a result, the scientists were able to create a “nano-robot” made of three DNA origami structures. It is consequently comparable in size to a human cell, being nanometric in size. The force that can be applied and controlled with a resolution of 1 piconewton, or one trillionth of a Newton, is made possible for the first time. One Newton is equal to the force of a finger clicking on a pen. This is the first time that a self-assembling DNA-based object made by people can move with such accuracy.
The team started by attaching a mechanoreceptor-recognizing molecule to the robot. We were able to tell the robot to go to some of our cells so that we could apply forces to certain mechanoreceptors on the surface of the cells to make them work.
In order to better understand the molecular processes behind cell mechanosensitivity and identify new cell receptors responsive to mechanical stresses, such a tool is extremely beneficial for fundamental research. Researchers will also be able to get a better idea of when, during the application of force, important signaling pathways for a wide range of biological and pathological processes are activated at the cellular level by the robot.
“A significant technological development has been made with the construction of a robot that allows the application of piconewton forces both in vitro and in vivo. The robot’s biocompatibility, albeit advantageous for in vivo applications, can also be a weakness because it makes it susceptible to enzymes that might break down DNA. Therefore, the next stage will be to research ways to alter the robot’s surface to make it less vulnerable to the effects of enzymes. We’ll also look at alternative ways to activate our robot, such as employing a magnetic field, “Bellot makes a point.”
