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The Driving Force: Nuclear Mechanotransduction in Cellular Function, Fate, and Disease.
Annual Review of Biomedical Engineering ( IF 9.7 ) Pub Date : 2019-06-05 , DOI: 10.1146/annurev-bioeng-060418-052139
Melanie Maurer 1 , Jan Lammerding 1
Affiliation  

Cellular behavior is continuously affected by microenvironmental forces through the process of mechanotransduction, in which mechanical stimuli are rapidly converted to biochemical responses. Mounting evidence suggests that the nucleus itself is a mechanoresponsive element, reacting to cytoskeletal forces and mediating downstream biochemical responses. The nucleus responds through a host of mechanisms, including partial unfolding, conformational changes, and phosphorylation of nuclear envelope proteins; modulation of nuclear import/export; and altered chromatin organization, resulting in transcriptional changes. It is unclear which of these events present direct mechanotransduction processes and which are downstream of other mechanotransduction pathways. We critically review and discuss the current evidence for nuclear mechanotransduction, particularly in the context of stem cell fate, a largely unexplored topic, and in disease, where an improved understanding of nuclear mechanotransduction is beginning to open new treatment avenues. Finally, we discuss innovative technological developments that will allow outstanding questions in the rapidly growing field of nuclear mechanotransduction to be answered.

中文翻译:

驱动力:细胞功能,命运和疾病的核机械转导。

通过机械转导过程,细胞行为不断受到微环境力的影响,其中机械刺激迅速转化为生化反应。越来越多的证据表明,细胞核本身是一个机械反应元件,对细胞骨架力起反应并介导下游生化反应。核通过多种机制作出反应,包括部分展开,构象变化和核被膜蛋白的磷酸化。核进口/出口的调制;和染色质组织改变,导致转录变化。尚不清楚这些事件中的哪些呈现直接的机械转导过程,哪些发生在其他机械转导途径的下游。我们将认真审查和讨论核机械转导的最新证据,特别是在干细胞命运这一尚未被广泛探讨的话题的背景下,以及在疾病中,对核机械转导的更深入了解开始为治疗开辟新途径。最后,我们讨论了创新的技术发展,这些发展将使在快速发展的核机械传递领域中的未决问题得到解答。
更新日期:2020-04-21
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