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A “nano-robot” built entirely from 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 being researched serious by scientists from Inserm, CNRS and the University of Montpellier at the Center de Biologie Structurale de Montpellier[1]. This highly innovative “nano-robot” should make it possible to study more closely the mechanical forces applied at microscopic levels, crucial for many biological and pathological processes. It is described in a new study published in Communication Nature.

Our cells are subjected to mechanical forces exerted on a microscopic scale, triggering biological signals essential to many cellular processes involved in the normal functioning of our organism or in the development of diseases.

For example, the sensation of touch is partly conditioned by the application of mechanical forces on specific cellular receptors (the discovery of which this year was rewarded with the Nobel Prize in Physiology or Medicine). In addition to touch, these receptors sensitive to mechanical forces (called mechanoreceptors) regulate other key biological processes such as the constriction of blood vessels, the perception of pain, breathing or the detection of sound waves in the ear, etc

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

At present, 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 mechanisms, but they have a number of limitations. In particular, they are very expensive and do not allow several cellular receptors to be studied at the same time, which makes their use very time-consuming if a lot of data is to be collected.

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Structures d’origami d’ADN

In order to propose an alternative, the research team led by Inserm researcher Gaëtan Bellot at the Center for Structural Biology (Inserm/CNRS/University of Montpellier) decided to use the DNA origami method. This enables the self-assembly of 3D nanostructures in a predefined shape using the DNA molecule as the building material. 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” made up of three DNA origami structures. Nanometric in size, it is therefore compatible with the size of a human cell. It allows for the first time to apply and control a force with a resolution of 1 piconewton, or one trillionth of a Newton — with 1 Newton corresponding to the force of a finger clicking on a pen. This is the first time that a man-made, self-assembled DNA object can apply force with such precision.

The team started by coupling the robot to a molecule that recognizes a mechanoreceptor. This made it possible to direct the robot towards some of our cells and specifically apply forces to targeted mechanoreceptors located on the surface of the cells in order to activate them.

Such a tool is very valuable for fundamental research, as it could 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 also 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.

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“The design of a robot allowing in vitro et in vivo The application of piconewton forces responds to a growing demand from the scientific community and represents a major technological advance. However, the biocompatibility of the robot can be considered both as an advantage for in vivo applications, but can also represent a weakness with sensitivity to enzymes that can degrade DNA. Our next step will therefore be to study how to modify the surface of the robot so that it is less sensitive to the action of enzymes. We will also try to find other ways of activating our robot using, for example, a magnetic field. » underlines Bellot.

[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 Physiology and Experimental Medicine: Heart-Muscles Laboratory (CNRS/Inserm/University of Montpellier).

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