Mechanical forces are exerted on our cells at the microscopic scale. They trigger biological signals that are critical to many cellular processes involved in the normal function of our bodies or in the development of disease. For example, the sensation of touch depends in part on the mechanical forces applied to specific cellular receptors. In addition to touch, these mechanical force-sensitive receptors regulate other critical biological processes such as vasoconstriction, respiration, pain sensation, and even the detection of sound waves in the ear.
This dysfunction of cellular mechanosensitivity is actually involved in many diseases. Like cancer: cancer cells make sounds and continuously adapt to the mechanical properties of their microenvironment as they migrate through the body. This adaptation is possible because specific forces are detected by mechanoreceptors, which transmit information to the cytoskeleton.
Currently, our understanding of these molecular mechanisms involved in cellular mechanosensitivity is still very limited. Although some techniques are already available to apply controlled forces and to study these mechanisms, they have some limitations. In particular, they are very expensive and do not allow us to study several cellular receptors at a time, which makes their use a very time-consuming task if we want to collect a large amount of data.
DNA origami structures
To propose an alternative, a team of researchers from the Center for Structural Biology, led by Inserm researcher Gaëtan Bellot, decided to use the DNA origami method. This allows the self-assembly of three-dimensional nanostructures in a predefined form using DNA molecules as building materials. The technique has led to significant advances in the field of nanotechnology over the past decade.c
It has enabled the team to design a “nanobot” consisting of three DNA origami structures. Because of its nanoscale dimensions, it is compatible with the size of a human cell. It makes it possible for the first time to apply and control a force with a resolution of 1 piconewton, or one trillionth of a newton – one newton is equivalent to the force of a finger clicking a pen. This is the first time that a human-made, DNA-based, self-assembling object can apply force with this kind of precision.
First, the researchers combined the robot with a molecule that recognizes mechanoreceptors. This makes it possible to guide the robot to some of our cells and apply force specifically to target mechanoreceptors positioned on the cell surface to activate them.
Such a tool is valuable for basic research because it can be used to better understand the molecular mechanisms involved in cellular mechanosensitivity and to discover new cellular receptors that are sensitive to mechanical forces. Thanks to the robot, researchers will also be able to study more precisely at what moment many key signaling pathways for biological and pathological processes are activated at the cellular level when force is applied.