A 'nano-robot' built entirely from DNA to explore cell processes
Autonomous DNA Nano-winch activation of integrin signaling. A The transmembrane receptor integrin (blue) exists as a compact αβ heterodimer. Integrins transmit applied mechanical stresses, between 1 and 15 pN, and recruits additional proteins to assemble focal adhesions including Focal Adhesion Kinase (FAK), which becomes phosphorylated at residue Y397 after mechanical stimulation of integrin. Addition of two antibodies with donor, D, and acceptor, A, labels allows detection of phosphorylated FAK in a LRET assay. Both antibodies bind to phosphorylated FAK (Y397-P) eliciting a detectable high LRET signal, whereas only a single antibody binds in the absence of phosphorylation yielding a low LRET signal. B MCF-7 cells in suspension were 1, left untreated control, 2, incubated with RGD conjugated oligonucleotide, 3, incubated with cRGD functionalized Piston-cylinder origami, 4, incubated with non-functionalized Nano-winches, 5, incubated with cRGD functionalized Nano-winch. Cells were then lysed and FAK phosphorylation. The background signal, R0, of antibodies alone was subtracted from the signal of lysed cells in experimental and control conditions calculated from ratios of acceptor and donor fluorescence intensities, RAD. Results are the average of at least three independent experiments. Error bars represent the standard deviation, statistical significance was determined by one-way analysis of variance with comparison to the untreated control (***P < 0.001).>Nature Communications (2022). DOI: 10.1038/s41467-022-30745-2, https://www.nature.com/articles/s41467-022-30745-2

A tiny robot made from DNA is being used to study cell processes. It is the subject of serious research by scientists from Inserm, CNRS and Université de Montpellier at the Structural Biology Center in Montpellier. The study of the mechanical forces applied at tiny levels is important for many biological and pathological processes. A new study describes it.

Our cells are subject to mechanical forces on a small scale, triggering biological signals that are essential to many cell processes involved in the normal functioning of our body or in the development of diseases.

The feeling of touch is dependent on the application of mechanical forces on specific cells. The regulation of other biological processes such as blood vessel constriction, pain perception, breathing, and even the detection of sound waves in the ear, can be done with the help of the mechanoreceptors.

Cancer: cancer cells migrate within the body by sounding and constantly adapting to the mechanical properties of their microenvironment is one of the diseases caused by the malfunctioning of this cellular mechanosensitivity. The ability to adapt is possible because specific forces are detected by the cells.

We don't know much about the mechanisms involved in cell sensitivity. There are several technologies that can be used to apply controlled forces, but they have limitations. They are very expensive and don't allow us to study several cell receptors at the same time, which makes it very difficult to collect a large amount of data.

The structures are made of genes.

In order to propose an alternative, the research team decided to use the DNA origami method. The self-assembly of 3D nanostructures in a pre-defined form is possible thanks to this. The last ten years have seen major advances in the field of nanotechnology.

The researchers were able to design a "nano-robot". It is compatible with the size of a cell. It is possible for the first time to apply and control a force with a resolution of 1 Piconewton, with 1Newton corresponding to the force of a fingerClicking on a pen. This is the first time that a human-made object can apply force.

The team started by attaching the robot to a molecule It was possible to apply forces to the cells on the robot's surface in order to get them to respond.

It is very useful for basic research, as it can be used to better understand the mechanisms involved in cell sensitivity to mechanical forces. Key signaling pathways for many biological and pathological processes are activated at cell level when applying force.

The design of a robot that can be used to apply Piconewton forces is a major technological advancement. The biocompatibility of the robot can be seen as both an advantage and weakness, but it may also be a weakness with respect to the degradation of DNA. The next step will be to modify the robot's surface to make it less sensitive to the action of enzymes. We will use a magnetic field to find other modes of robot activation.

More information: A. Mills et al, A Modular Spring-Loaded Actuator for Mechanical Activation of Membrane Proteins, Nature Communications (2022). DOI: 10.1038/s41467-022-30745-2, www.nature.com/articles/s41467-022-30745-2 Journal information: Nature Communications