完全由DNA構建的"納米機器人"用於探索細胞過程

A “Nano-Robot” Built Entirely from DNA to Explore Cell Processes！- Prepare For Change

完全由DNA構建的"納米機器人"用於探索細胞過程！- Prepare For Change

By Derek Knauss - July 31, 2022，From presse.inser.fr:

作者：Derek Knauss - 7月31日, 2022，來自presse.inser.fr。

Press release | 28 Jul 2022 – 11h00 | By INSERM PRESS OFFICE
新聞稿 | 2022年7月28日 - 11h00 | 由INSERM新聞辦公室發布

Molecular and structural bases of living organisms | Health technologies
生物體的分子和結構基礎 | 健康技術

Constructing a tiny robot from DNA and using it to study cell processes invisible to the naked eye… You would be forgiven for thinking it is science fiction, but it is in fact the subject of serious research by scientists from Inserm, CNRS and Université de Montpellier at the Structural Biology Center in Montpellier[1]. This highly innovative “nano-robot” should enable closer study of the mechanical forces applied at microscopic levels, which are crucial for many biological and pathological processes. It is described in a new study published in Nature Communications.

用DNA構建一個微小的機器人，用它來研究肉眼看不見的細胞過程...... 你可以理解為這是科幻小說，但它實際上是來自 Inserm、CNRS 和蒙彼利埃大學的科學家在蒙彼利埃結構生物學中心的嚴肅研究課題 [1]。這種高度創新的"納米機器人"應該能夠更密切地研究施加在微觀層面的機械力，這對許多生物和病理過程至關重要。自然通訊》上發表的一項新研究對它進行了描述。

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

我們的細胞受到在微觀尺度上施加的機械力的影響，觸發了對參與我們身體正常運作或疾病發展的許多細胞過程至關重要的生物信號。

For example, the feeling of touch is partly conditional on the application of mechanical forces on specific cell receptors (the discovery of which was this year rewarded by the Nobel Prize in Physiology or Medicine).

例如，觸摸的感覺部分取決於對特定細胞受體施加的機械力（這一發現在今年獲得了諾貝爾生理學或醫學獎）。

In addition to touch, these receptors that are sensitive to mechanical forces (known as mechanoreceptors) enable the regulation of other key biological processes such as blood vessel constriction, pain perception, breathing or even the detection of sound waves in the ear, etc.

除了觸覺之外，這些對機械力敏感的受體（被稱為機械感受器）還能調節其他關鍵的生物過程，如血管收縮、痛覺、呼吸甚至耳朵裡的聲波探測等等。

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

這種細胞機械敏感性的功能障礙涉及許多疾病 -- 例如癌症：癌細胞在體內遷移時，會發出聲音並不斷適應其微環境的機械特性。這種適應是可能的，因為特定的力是由機械感受器探測到的，而機械感受器將信息傳遞給細胞骨架。

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 a number of limitations. In particular, they are very costly and do not allow us to study several cell receptors at a time, which makes their use very time-consuming if we want to collect a lot of data.

目前，我們對參與細胞機械敏感性的這些分子機制的了解仍然非常有限。已經有一些技術可以應用受控的力並研究這些機制，但它們有一些限制。特別是，它們非常昂貴，而且不允許我們一次研究幾個細胞受體，這使得如果我們想收集大量的數據，使用它們非常耗時。

 

DNA origami structures
DNA摺紙結構

In order to propose an alternative, the research team led by Inserm researcher Gaëtan Bellot at the Structural Biology Center (Inserm/CNRS/Université de Montpellier) decided to use the DNA origami method. This enables the self-assembly of 3D nanostructures in a pre-defined form using the DNA molecule as construction material. Over the last ten years, the technique has allowed major advances in the field of nanotechnology.

為了提出一個替代方案，由Inserm研究人員Gaëtan Bellot領導的結構生物學中心（Inserm/CNRS/蒙彼利埃大學）的研究小組決定使用DNA摺紙方法。這使得三維納米結構的自我組裝能夠以預先定義的形式使用DNA分子作為建築材料。在過去的十年裡，該技術使納米技術領域取得了重大進展。

This enabled the researchers to design a “nano-robot” composed of three DNA origami structures. Of nanometric 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, namely 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 human-made, self-assembled DNA-based object can apply force with this accuracy.

這使研究人員能夠設計一個由三個DNA摺紙結構組成的"納米機器人"。其大小為納米級，因此與人體細胞的大小相符。它使人們首次有可能應用和控制分辨率為1皮克牛頓的力，即一萬億分之一的牛頓 -- 1牛頓相當於手指點擊筆的力量。這是第一次人類製造的、基於DNA的自組裝物體能夠以這種精度施力。

The team began by coupling the robot with a molecule that recognizes a mechanoreceptor. This made it possible to direct the robot to some of our cells and specifically apply forces to targeted mechanoreceptors localized on the surface of the cells in order to activate them. Such a tool is very valuable for basic research, as it could be used to better understand the molecular mechanisms involved in cell mechanosensitivity and discover new cell receptors sensitive to mechanical forces. Thanks to the robot, the scientists will also be able to study more precisely at what moment, when applying force, key signaling pathways for many biological and pathological processes are activated at cell level.

該團隊首先將機器人與一個能識別機械感受器的分子相連接。這使得機器人有可能被引導到我們的一些細胞上，並專門向細胞表面的目標機械感受器施力，以激活它們。這樣的工具對基礎研究非常有價值，因為它可以用來更好地理解涉及細胞機械敏感性的分子機制，並發現對機械力敏感的新細胞受體。由於該機器人，科學家們還將能夠更精確地研究在什麼時刻，當施力時，許多生物和病理過程的關鍵信號通路在細胞水平被激活。

“THE DESIGN OF A ROBOT ENABLING THE IN VITRO AND IN VIVO APPLICATION OF PICONEWTON FORCES MEETS A GROWING DEMAND IN THE SCIENTIFIC COMMUNITY AND REPRESENTS A MAJOR TECHNOLOGICAL ADVANCE. HOWEVER, THE BIOCOMPATIBILITY OF THE ROBOT CAN BE CONSIDERED BOTH AN ADVANTAGE FOR IN VIVO APPLICATIONS BUT MAY ALSO REPRESENT A WEAKNESS WITH SENSITIVITY TO ENZYMES THAT CAN DEGRADE DNA. SO OUR NEXT STEP 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 USING, FOR EXAMPLE, A MAGNETIC FIELD,” EMPHASIZES BELLOT.

"設計一個能夠在體外和體內應用皮克牛頓力的機器人滿足了科學界日益增長的需求，並代表了一項重大的技術進步。然而，該機器人的生物相容性既可以被認為是體內應用的優勢，但也可能是對可降解DNA的酶敏感的弱點。因此，我們的下一步將是研究如何修改機器人的表面，使其對酶的作用不那麼敏感。我們還將嘗試尋找其他激活機器人的模式，例如使用磁場”。BELLOT 強調說。

 

[1] Also contributed to this research: the Institute of Functional Genomics (CNRS/Inserm/Université de Montpellier), the Max Mousseron Biomolecules Institute (CNRS/Université de Montpellier/ENSCM), the Paul Pascal Research Center (CNRS/Université de Bordeaux) and the Physiology and Experimental Medicine: Heart-Muscles laboratory (CNRS/Inserm/Université de Montpellier).

[1] 為這項研究做出貢獻的還有：功能基因組學研究所（CNRS/Inserm/蒙彼利埃大學）、Max Mousseron生物分子研究所（CNRS/蒙彼利埃大學/ENSCM）、保羅-帕斯卡爾研究中心（CNRS/波爾多大學）以及生理學和實驗醫學。心肌實驗室（CNRS/Inserm/Université de Montpellier）。

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原文：https://prepareforchange.net/2022/07/31/a-nano-robot-built-entirely-from-dna-to-explore-cell-processes/