Creating a tiny DNA-based robot to investigate cell processes that are invisible to the human eye… You might be forgiven for thinking it is science fiction, but it is the subject of substantial research being undertaken at the Structural Biology Center in Montpellier by Inserm, CNRS, and Université de Montpellier researchers. This ultra-advanced “nano-robot” might make it feasible to examine mechanical forces at microscopic sizes, which are crucial for many biological and pathological processes, in greater detail. Recent study published in Nature Communications provides specifics.
Micromechanical forces acting on our cells transmit biological signals that are essential to a variety of cell processes involved in the development of diseases or the normal functioning of our bodies.
For example, the feeling of touch is somewhat dependent on the application of mechanical pressures to certain cell receptors (the discovery of which was this year rewarded by the Nobel Prize in Physiology or Medicine). These touch-sensitive sensors, known as mechanoreceptors, also allow for the regulation of other essential biological functions, such as blood vessel constriction, pain perception, breathing, and even the detection of sound waves in the ear.
The failure of this cellular mechanosensitivity is associated with several diseases, including cancer. By vibrating and continuously responding to the mechanical features of their surroundings, cancer cells spread throughout the body. This adaptation is only possible when mechanoreceptors identify specific forces and relay this information to the cytoskeleton.
We now have a limited understanding of the molecular mechanisms underpinning cell mechanosensitivity. For the application of controlled forces and the study of these systems, a number of technologies are already accessible, but with numerous limitations. Due to the fact that we cannot evaluate several cell receptors simultaneously, their use is both costly and time-consuming if we need to collect a large amount of data.
Origami DNA structures
In order to provide a replacement, the research team at the Structural Biology Center (Inserm/CNRS/Université de Montpellier), led by Inserm researcher Gatan Bellot, decided to use the DNA origami approach. This enables DNA molecules to act as the building blocks for self-assembling 3D nanostructures with a specified form. In the last decade, the approach has permitted substantial advances in the area of nanotechnology.
Thus, the scientists were able to construct a “nano-robot” composed of three DNA origami structures. It is thus equivalent in size to a human cell, since its dimensions are nanometric. For the first time, it is possible to apply and regulate a force with a resolution of 1 piconewton, or one trillionth of a Newton. 1 Newton is equivalent to the force exerted when a finger clicks a pen. This is the first time that a self-assembled DNA-based object produced by humans can apply such precise force.
The scientists began by connecting a molecule capable of identifying mechanoreceptors to the robot. This enabled us to drive the robot to certain cells in order to selectively apply forces to mechanoreceptors placed on the surface of the cells to activate them.
In order to better comprehend the molecular mechanisms behind cell mechanosensitivity and to uncover new cell receptors sensitive to mechanical stressors, such a tool is very advantageous for basic research. Researchers will also be able to identify with more precision when, during the application of force, crucial signalling pathways for a range of biological and pathological processes are activated at the cellular level.
“The design of a robot that enables the application of piconewton pressures in vitro and in vivo is a substantial technological advancement. The biocompatibility of the robot, although favourable for in vivo applications, might be disadvantageous since it renders it sensitive to enzymes that can degrade DNA. Therefore, the next step will be to investigate methods to modify the surface of the robot to make it less susceptible to the impacts of enzymes. We will also investigate other activation methods for our robot, such as using a magnetic field “Bellot makes a point.
This work was also supported by the Max Mousseron Biomolecules Institute (CNRS/Université de Montpellier/ENSCM), the Paul Pascal Research Center (CNRS/Université de Bordeaux), and the Physiology and Experimental Medicine: Heart-Muscles laboratory (CNRS/Inserm/Université de Montpellier).