Our cells are subject to tiny mechanical stresses. They set off biological signals that are crucial for numerous cell processes involved in either the development of illnesses or the regular operation of our bodies.
For instance, the sensation of touch depends in part on the application of mechanical forces to certain cell receptors (the discovery of which was rewarded this year by the Nobel Prize in Physiology or Medicine). These touch-sensitive receptors, or mechanoreceptors, are also involved in breathing, pain perception, blood vessel constriction, and even the detection of sound waves in the ear, among other important biological functions.
In fact, many illnesses are influenced by cellular mechanosensitivity deficiency. For instance, in cancer, cancer cells sound as they move throughout the body, continually adjusting to the mechanical characteristics of their surroundings. Only because certain forces are identified by mechanoreceptors, which then pass the information to the cell cytoskeleton, is such adaptation feasible.
We now know relatively little about the molecular processes underlying cell mechanosensitivity. To apply regulated forces and research these systems, a variety of technologies are currently available, although they have several drawbacks. They are particularly expensive and time-consuming to utilize if we want to gather a lot of data due to the fact that we cannot analyze several cell receptors at once.
The Structural Biology Center team at Inserm/CNRS/Université de Montpellier chose to employ the DNA origami technique to present a substitute, under the direction of Inserm researcher Gatan Bellot. This makes it possible for the DNA molecule to self-assemble 3D nanostructures in a pre-determined shape. The method has enabled significant advancements in the field of nanotechnology during the past 10 years.
As a result, the group was able to create a “nano-robot” made of three DNA origami structures. It is suitable with the size of a human cell since it is 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 feasible for the first time. 1 Newton is equal to the force of a finger clicking on a pen. This is the first time that a self-assembled DNA-based device that was created by humans can exert force with such accuracy.
The researchers first connected the robot to a chemical that can identify a mechanoreceptor. This enabled it feasible to direct the robot to certain of our cells and apply precise pressures to activate selected mechanoreceptors that were located on the surface of the cells.
In order to better understand the molecular processes behind cell mechanosensitivity and identify novel cell receptors responsive to mechanical stresses, such a tool is extremely beneficial for fundamental research. The robot will also enable researchers to more accurately determine when, during the application of force, important signaling pathways for various biological and pathological processes are engaged at the cellular level.
“A increasing need in the scientific community is being met by the construction of a robot that can apply piconewton pressures both in vitro and in vivo, which is a significant technical advancement. The robot’s biocompatibility, albeit advantageous for in vivo applications, can also be a drawback 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 into alternative ways to activate our robot, such as by employing a magnetic field, Bellot says.