Functional proteomics of cellular mechanosensing mechanisms.
Functional proteomics of cellular mechanosensing mechanisms.
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DOI：
10.1016/j.semcdb.2017.06.019
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发表时间：
2017-11
影响因子：
7.3
通讯作者：
A. Wasik;H. Schiller
中科院分区：
文献类型：
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作者：
A. Wasik;H. Schiller
机械传感使细胞能够协调其表型与其组织微环境的机械特性。在这个过程中，细胞通过施加收缩力来探测它们的周围环境，这在细胞内产生不同量的机械应变，作为它们的细胞外基质的刚度的函数。然后，细胞内的张力可以影响大多数细胞器的结构和组成，包括细胞粘附、细胞骨架、质膜和细胞核。在分子水平上，蛋白质的构象，修饰，相互作用和亚细胞定位已被证明是由生物力学力改变。功能蛋白质组学的目的是在蛋白质组范围内，无偏见和高通量的方式分析这些影响。新兴的方法，如交联质谱和先进的蛋白质相关性分析，将使未来的分析mechanosensing的水平上的蛋白质相互作用in situ和亚细胞蛋白质定位，现在可以确定非常高的准确性，从全细胞分析数以千计的蛋白质一次。结合使用这些质谱工具集与翻译后修饰的分析，最终将该领域移动到细胞机械传感中分子改变的全面列表。我们将对功能蛋白质组学的最新发展和在机械生物学相关问题上的最新应用进行概述。
Mechanosensing enables cells to coordinate their phenotype with the mechanical properties of their tissue microenvironment. In this process, cells probe their surroundings by applying contractile forces, which produces different amounts of mechanical strain within the cells as a function of the stiffness of their extracellular substrates. Tension within cells can then affect the structure and composition of most cellular organelles, including cell adhesions, the cytoskeleton, the plasma membrane and the nucleus. On a molecular level, the conformations, modifications, interactions, and subcellular localizations of proteins have been shown to be altered by biomechanical forces. Functional proteomics aims at the analysis of these effects in a proteome wide, unbiased and high throughput manner. Emerging methods, such as crosslinking mass spectrometry and advanced protein correlation profiling, will enable future analysis of mechanosensing on the level of protein interactionsin situ, and subcellular protein localization, which can now be determined with very high accuracy from whole cell analysis for thousands of proteins at once. Combined use of these mass spectrometry toolsets with the analysis of posttranslational modifications will ultimately move the field to a comprehensive list of molecular alterations in cellular mechanosensing. We will give an overview on current developments in functional proteomics and the latest applications on questions related to mechanobiology.