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In-cell NMR: Why and how?
Progress in Nuclear Magnetic Resonance Spectroscopy ( IF 6.1 ) Pub Date : 2022-05-04 , DOI: 10.1016/j.pnmrs.2022.04.002
Francois-Xavier Theillet 1 , Enrico Luchinat 2
Affiliation  

NMR spectroscopy has been applied to cells and tissues analysis since its beginnings, as early as 1950. We have attempted to gather here in a didactic fashion the broad diversity of data and ideas that emerged from NMR investigations on living cells. Covering a large proportion of the periodic table, NMR spectroscopy permits scrutiny of a great variety of atomic nuclei in all living organisms non-invasively. It has thus provided quantitative information on cellular atoms and their chemical environment, dynamics, or interactions. We will show that NMR studies have generated valuable knowledge on a vast array of cellular molecules and events, from water, salts, metabolites, cell walls, proteins, nucleic acids, drugs and drug targets, to pH, redox equilibria and chemical reactions. The characterization of such a multitude of objects at the atomic scale has thus shaped our mental representation of cellular life at multiple levels, together with major techniques like mass-spectrometry or microscopies.

NMR studies on cells has accompanied the developments of MRI and metabolomics, and various subfields have flourished, coined with appealing names: fluxomics, foodomics, MRI and MRS (i.e. imaging and localized spectroscopy of living tissues, respectively), whole-cell NMR, on-cell ligand-based NMR, systems NMR, cellular structural biology, in-cell NMR… All these have not grown separately, but rather by reinforcing each other like a braided trunk. Hence, we try here to provide an analytical account of a large ensemble of intricately linked approaches, whose integration has been and will be key to their success.

We present extensive overviews, firstly on the various types of information provided by NMR in a cellular environment (the “why”, oriented towards a broad readership), and secondly on the employed NMR techniques and setups (the “how”, where we discuss the past, current and future methods). Each subsection is constructed as a historical anthology, showing how the intrinsic properties of NMR spectroscopy and its developments structured the accessible knowledge on cellular phenomena. Using this systematic approach, we sought i) to make this review accessible to the broadest audience and ii) to highlight some early techniques that may find renewed interest. Finally, we present a brief discussion on what may be potential and desirable developments in the context of integrative studies in biology.



中文翻译:

细胞内核磁共振:为什么以及如何?

早在 1950 年,核磁共振波谱学就已应用于细胞和组织分析。我们试图以一种说教的方式收集从活细胞核磁共振研究中产生的广泛多样性的数据和想法。核磁共振波谱涵盖了元素周期表的很大一部分,可以无创地检查所有生物体中的各种原子核。因此,它提供了关于细胞原子及其化学环境、动力学或相互作用的定量信息。我们将展示 NMR 研究已经产生了关于大量细胞分子和事件的宝贵知识,从水、盐、代谢物、细胞壁、蛋白质、核酸、药物和药物靶标,到 pH 值、氧化还原平衡和化学反应。

细胞核磁共振研究伴随着核磁共振成像和代谢组学的发展,各种子领域蓬勃发展,并创造了吸引人的名字:通量组学、食品组学、核磁共振成像和磁共振成像(分别是活组织的成像和局部光谱学)、全细胞核磁共振、关于-基于细胞配体的核磁共振、系统核磁共振、细胞结构生物学、细胞内核磁共振……所有这些都没有单独生长,而是像编织树干一样相互加强。因此,我们在这里尝试提供对大量错综复杂的方法的分析说明,这些方法的整合已经并将成为它们成功的关键。

我们提供广泛的概述,首先是关于 NMR 在细胞环境中提供的各种类型的信息(“为什么”,面向广大读者),其次是所采用的 NMR 技术和设置(“如何”,我们讨论的地方过去、现在和未来的方法)。每个小节都是作为历史选集构建的,展示了核磁共振光谱的内在特性及其发展如何构建关于细胞现象的可访问知识。使用这种系统的方法,我们寻求 i) 让最广泛的受众可以访问这篇评论,以及 ii) 突出一些可能会重新引起人们兴趣的早期技术。最后,我们简要讨论了在生物学综合研究的背景下什么是潜在的和可取的发展。

更新日期:2022-05-06
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