A “nano-robot” made entirely of DNA to explore cellular processes

Building a tiny robot out of DNA and using it to study cellular processes invisible to the naked eye… we’d be forgiven for thinking it’s science fiction, but it’s actually serious research being done by scientists at INSERM, CNRS and the University of Montpellier. Center de biology structural de Montpellier[1]. This highly innovative “nano-robot” will make it possible to study more closely the mechanical forces applied at the microscopic level, which are important for many biological and pathological processes. This is described in a new study published Nature communication.

Our cells are subjected to mechanical forces applied on a microscopic scale, which trigger biological signals necessary for many cellular processes involved in the normal functioning of our organism or the development of disease.

For example, the sensation of touch is partially conditioned by the application of mechanical force to specific cellular receptors (the discovery of which was awarded this year with the Nobel Prize in Physiology or Medicine). Apart from touch, these receptors sensitive to mechanical forces (called mechanoreceptors) control other important biological processes such as constriction of blood vessels, perception of pain, respiration or detection of sound waves in the ear.

Dysfunction of this cellular mechanosensitivity is involved in many diseases, for example cancer: cancerous cells make noise and migrate inside the organism, constantly adapting to the mechanical properties of their microenvironment. Such adaptation is only possible because specific forces are detected by mechanoreceptors that transmit information to the cellular cytoskeleton.

Currently, our knowledge of these molecular mechanisms involved in cellular mechanosensitivity is still very limited. Several technologies are already available to apply controlled forces and study these processes, but they have several limitations. In particular, they are very expensive and do not allow studying multiple cellular receptors at the same time, which makes their use very time-consuming if large amounts of data are to be collected.

DNA origami structure

To propose an alternative, the research team led by Inserm researcher Gaëtan Bellot of the Center for Structural Biology (Inserm/CNRS/University of Montpellier) decided to use the DNA origami method. It enables the self-assembly of 3D nanostructures into predetermined shapes using DNA molecules as building blocks. Over the past ten years, the technique has enabled major advances in the field of nanotechnology.

This allowed the researchers to design a “nano-robot” consisting of three DNA origami structures. It is nanometric in size, so it corresponds to the size of a human cell. This allows for the first time to apply and control a force with a resolution of 1 piconewton, or one trillionth of a newton – where 1 newton corresponds to the force of a finger clicking a pen. This is the first time that a man-made, self-assembling DNA object can exert force with such precision.

The team started by attaching the robot to a molecule that recognizes a mechanoreceptor. This allows us to point the robot at certain cells and apply forces specifically to targeted mechanoreceptors located on the cell surface to activate them.

Such a tool is extremely valuable for basic research, as it can be used to better understand the molecular mechanisms involved in cellular mechanosensitivity and to discover new cellular receptors sensitive to mechanical forces. Thanks to the robot, scientists will be able to study more precisely when, during the application of force, the key signaling pathways of many biological and pathological processes are activated at the cellular level.

“The design of a robot allows in vitro And show live The application of piconewton forces responds to the growing needs of the scientific community and represents a major technological advance. However, the biocompatibility of the robot can be considered an advantage for both show live applications, but may also present a vulnerability with sensitivity to enzymes that can degrade DNA. So our next step will be to study how to modify the surface of the robot so that it is less sensitive to enzyme activity. We will also try to find other ways to activate our robot, for example, a magnetic field. » Underline the ballot.

[1] Also contributing to this research: the Institute of Functional Genomics (CNRS/Inserm/University of Montpellier), the Max Mousseron Biomolecules Institute (CNRS/University of Montpellier/ENSCM), the Paul Pascal Research Center (CNRS/University of Bordeaux) and the Physiology and Experimental Medicine: Heart-Muscles Laboratory (CNRS/Inserm/Montpellier University).

Leave a Comment