A DNA-based nano-robot to explore your cells

Better understand various processes invisible toeye bare, which take place on the scale of our cells, thanks to a tiny robot built on the basis of DNA… If this is almost like a project of science fictionit is in fact very serious work carried out by researchers from Inserm, CNRS and the University of Montpellier at the Structural Biology Center of Montpellier[1]. This very innovative “nano-robot” should make it possible to study more closely the mechanical forces which apply at microscopic levels and which are crucial for many biological processes and pathological. The device is described in a new study, published in the journal NatureCommunications.

Mechanical forces are exerted on a microscopic scale on our cellstriggering biological signals that are essential for many cellular processes involved in the normal functioning of our organism or in the development of pathologies. For example, the sensation of touch is partly conditioned by theapplication mechanical forces on specific cellular receptors (the discovery of which was rewarded this year by the Nobel Prize in Medicine). In addition to touch, these receptors sensitive to mechanical forces (we speak of mechano-receptors) allow the regulation of other key biological processes such as the constriction of blood vessels, the perception of pain, breathing or even detecting sound waves in the ear, etc.

The dysfunction of this cellular mechano-sensitivity is particularly involved in many pathologies such as cancer: cancer cells migrate through the body by constantly probing and adapting to the mechanical properties of their microenvironment. This adaptation can only take place because specific forces are detected by mechano-receptors which transmit the information to the cell cytoskeleton.

At present, our knowledge of these molecular mechanisms involved in cellular mechano-sensitivity is still very limited. Several technologies are already available to apply controlled forces and study these mechanisms, but they have a number of limitations. They are in particular very expensive and do not make it possible to study several cellular receptors at the same time, which means that they are very time-consuming to use if one wishes to collect numerous data.

A molecular actuator made from DNA origami

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 allows the self-assembly of 3D nanostructures in a predefined shape using the molecule of DNA as material for construction. Over the past ten years, the technique has enabled major advances in the field of nanotechnology.

The researchers thus succeeded in designing a “nano-robot” made up of three DNA origami. 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 thousand-billionth of Newton, a Newton corresponding to the force of a finger on the plunger of the pen. This is the first time that a self-assembled, human-made DNA object can apply force with such precision.

First, the robot is coupled with a molecule which recognizes a mechano-receptor. This coupling then makes it possible to direct the robot on some of our cells and specifically apply forces on the cellular mechano-receptors targeted and 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 mechano-sensitivity and to discover new cellular receptors sensitive to mechanical forces. Using the robot, scientists will also be able to study more precisely when, upon application of force, key signaling pathways for many biological and pathological processes activate at the cell level.

” The design of a robot that allows the application of forces of the order of the piconewton in vitro and live responds to a growing demand in the scientific community and represents an important technological advance. On the other hand, the biocompatibility of the robot can be considered both as an advantage for applications live but can also represent a weakness with sensitivity to enzymes which can degrade DNA, emphasizes Gaëtan Bellot. So the next stage of our work will be to study how we can modify the surface of the robot so that it is less sensitive to the action of enzymes. We will also try to find other modes of activation of our robot by using for example a magnetic field “.

[1] The Institute of genomics (CNRS/Inserm/University of Montpellier), the Max Mousseron Institute of Biomolecules (CNRS/University of Montpellier/ENSCM), the Paul Pascal Research Center (CNRS/University of Bordeaux) and the Heart Physiology and Experimental Medicine Laboratory and muscles (CNRS/Inserm/University of Montpellier.