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 was science fiction, but it is actually the focus of significant research being conducted at the Structural Biology Center in Montpellier by professionals from Inserm, CNRS, and Université de Montpellier. This extremely cutting-edge “nano-robot” could make it possible to analyse 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.
Micromechanical forces acting on our cells cause biological signals that are crucial to numerous cell processes involved in either the development of diseases or the regular operation of our bodies. 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 characterised 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 particular 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 number of technologies are already available, although they have several drawbacks. They are particularly expensive and time-consuming to utilise if we want to gather a lot of data due to the fact that we cannot analyse multiple cell receptors at once.
DNA origami structures
The research group at the Structural Biology Center (Inserm/CNRS/Université de Montpellier), lead 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 in a predetermined shape. The method has enabled significant advancements in the field of nanotechnology over the past ten years.
As a result, the scientists were able to create a “nano-robot” made of three DNA origami structures. It is therefore 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. 1 Newton is equal to the force of a finger clicking on a pen. This is the first time a self-assembled DNA-based object that was created by humans can exert force with such precision.
The team started by attaching a mechanoreceptor-recognizing molecule to the robot. In order to specifically apply forces to particular mechanoreceptors located on the surface of the cells in order to activate them, this allowed us to direct the robot to some of our cells. The team started by attaching a mechanoreceptor-recognizing molecule to the robot. In order to specifically apply forces to particular mechanoreceptors located on the surface of the cells in order to activate them, this allowed us to direct the robot to some of our cells.
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. The robot will also enable researchers to more accurately determine when, during the application of force, important signalling pathways for a variety of biological and pathological processes are triggered at the cellular level.
“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 employing a magnetic field, “Bellot makes a point.