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A ‘nano-robot’ built entirely from DNA to explore cell processes

Een 'nano-robot' volledig opgebouwd uit DNA om celprocessen te onderzoeken0of 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. The 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). Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-30745-2, https://www.nature.com/articles/s41467-022-30745-2″ width=”800″ height=”358″/>

Autonomic DNA Nano-lier Activation of Integrin Signaling. A The transmembrane receptor integrin (blue) exists as a compact αβ-heterodimer. Integrins emit applied mechanical stresses, between 1 and 15 pN, and recruit additional proteins to assemble focal adhesions, including Focal Adhesion Kinase (FAK), which is phosphorylated at residue Y397 upon mechanical stimulation of integrin. Addition of two antibodies with donor, D, and acceptor, A, labels allows for detection of phosphorylated FAK in a LRET assay. Both antibodies bind to phosphorylated FAK (Y397-P) and elicit a detectably high LRET signal, while only a single antibody binds in the absence of phosphorylation, yielding a low LRET signal. B MCF-7 cells in suspension were 1, 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, R0of antibodies alone was subtracted from the signal from lysed cells in experimental and control conditions calculated from ratios of acceptor and donor fluorescence intensities, RADVERTISEMENT. The results are the average of at least three independent experiments. Error bars represent standard deviation, statistical significance was determined by one-way analysis of variance with comparison to the untreated control (***P Nature Communications (2022). DOI: 10.1038/s41467-022-30745-2, https://www.nature. com/articles/s41467-022-30745-2

Building a tiny robot from DNA and using it to study cell processes invisible to the naked eye… You might think it’s science fiction, but it’s in fact the subject of serious research by scientists from Inserm, CNRS, and Université de Montpellier at the Structural Biology Center in Montpellier. This highly innovative “nano-robot” should allow a closer examination of the mechanical forces exerted at microscopic levels, which are crucial for many biological and pathological processes. It is described in a new study published in nature communication.

Our cells are subject to mechanical forces exerted on a microscopic scale, activating biological signals that are essential for many cell processes involved in the normal functioning of our bodies or in the development of diseases.

For example, the sense of touch is partly dependent on the application of mechanical forces to specific cell receptors (the discovery of which was awarded this year’s Nobel Prize in Physiology or Medicine). In addition to touch, these receptors that are sensitive to mechanical forces (known as mechanoreceptors) allow the regulation of other important biological processes such as blood vessel constriction, pain perception, breathing or even the detection of sound waves in the ear, etc.

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

At present, our knowledge of these molecular mechanisms involved in cell mechanosensitivity is still very limited. Several technologies are already available to apply controlled forces and study these mechanisms, but they have some limitations. In particular, they are very expensive and do not allow us to study multiple cell receptors at the same time, which makes their use very time-consuming if we want to collect a lot of data.

DNA origami structures

To propose an alternative, the research team led by Inserm researcher Gaëtan Bellot of the Structural Biology Center (Inserm/CNRS/Université de Montpellier) decided to use the DNA origami method. This allows the self-assembly of 3D nanostructures in a predefined shape using the DNA molecule as construction material. Over the past ten years, technology has enabled major advances in nanotechnology.

This allowed the researchers to design a “nano-robot” made up of three DNA origami structures. Being nanometric in size, it is therefore 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, which is one trillionth of a Newton – where 1 Newton corresponds to the force of a finger clicking a pen. This is the first time a man-made, self-assembled DNA-based object has been able to exert force with this accuracy.

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

Such a tool is very valuable for basic research because it can be used to better understand the molecular mechanisms involved in the mechanosensitivity of cells and to discover new cell receptors that are sensitive to mechanical forces. The robot will also allow the scientists to study more closely at what point, when force is applied, key signaling pathways for many biological and pathological processes are activated at the cellular level.

“The design of a robot that enables the in vitro and in vivo application of piconewton forces responds to a growing demand in the scientific community and represents an important technological advancement. However, the biocompatibility of the robot can be considered as an advantage for in vivo applications, but can also be a weakness with susceptibility to enzymes that can break down DNA. So our next step will be to explore how we can modify the surface of the robot so that it is less sensitive to the action of enzymes. We will also try other activation modes of our robot using, for example, a magnetic field,” says Bellot.

What the mechanical forces behind protein folding can tell us about metastatic cancer?

More information:
A. Mills et al, a modular spring-loaded actuator for mechanical activation of membrane proteins, nature communication (2022). DOI: 10.1038/s41467-022-30745-2, www.nature.com/articles/s41467-022-30745-2

Provided by Institut National de la Sante et de la Recherche Medicale

Quote: A ‘nano-robot’ built entirely from DNA to explore cell processes (2022, July 28) retrieved July 28, 2022 from https://phys.org/news/2022-07-nano-robot-built-dna-explore – cell.html

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