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The Next Frontier: Quantitative Biochemistry in Living Cells
Biochemistry ( IF 2.9 ) Pub Date : 2017-12-18 00:00:00 , DOI: 10.1021/acs.biochem.7b01060
Alf Honigmann 1 , André Nadler 1
Affiliation  

Researchers striving to convert biology into an exact science foremost rely on structural biology and biochemical reconstitution approaches to obtain quantitative data. However, cell biological research is moving at an ever-accelerating speed into areas where these approaches lose much of their edge. Intrinsically unstructured proteins and biochemical interaction networks composed of interchangeable, multivalent, and unspecific interactions pose unique challenges to quantitative biology, as do processes that occur in discrete cellular microenvironments. Here we argue that a conceptual change in our way of conducting biochemical experiments is required to take on these new challenges. We propose that reconstitution of cellular processes in vitro should be much more focused on mimicking the cellular environment in vivo, an approach that requires detailed knowledge of the material properties of cellular compartments, essentially requiring a material science of the cell. In a similar vein, we suggest that quantitative biochemical experiments in vitro should be accompanied by corresponding experiments in vivo, as many newly relevant cellular processes are highly context-dependent. In essence, this constitutes a call for chemical biologists to convert their discipline from a proof-of-principle science to an area that could rightfully be called quantitative biochemistry in living cells. In this essay, we discuss novel techniques and experimental strategies with regard to their potential to fulfill such ambitious aims.

中文翻译:

下一个领域:活细胞中的定量生物化学

致力于将生物学转变为一门精确科学的研究人员,主要依靠结构生物学和生化重建方法来获得定量数据。但是,细胞生物学研究正以越来越快的速度向这些方法失去优势的领域发展。本质上非结构化的蛋白质和由可互换,多价和非特异性相互作用组成的生化相互作用网络对定量生物学构成了独特的挑战,在离散的细胞微环境中发生的过程也是如此。在这里,我们认为,进行生化实验的方式必须进行观念上的改变,以应对这些新挑战。我们建议体外细胞过程的重建应更多地集中在模仿细胞环境在体内,这是一种需要详细了解细胞隔室的材料特性的方法,本质上需要细胞的材料科学。同样,我们建议体外定量生化实验应与体内相应实验同时进行,因为许多新近相关的细胞过程高度依赖于上下文。从本质上讲,这呼吁化学生物学家将其学科从原理证明科学转变为可以被称为活细胞定量生物化学的领域。在本文中,我们将讨论新颖的技术和实验策略,以实现其雄心勃勃的目标。
更新日期:2017-12-18
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