Swift Joe, Discher Dennis E
Molecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Molecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA
J Cell Sci. 2014 Jul 15;127(Pt 14):3005-15. doi: 10.1242/jcs.149203. Epub 2014 Jun 24.
How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage.
多年来，细胞如何响应物理信号以适应并承受其周围环境的物理需求一直备受关注，当前的研究工作集中在将信号转化为基因表达的机制上。机械调节转录因子进入细胞核的途径正在兴起，我们最近的研究表明，在成熟组织和发育中的组织中，细胞核自身的机械特性会根据细胞外基质（ECM）的弹性而受到主动调控。在本评论中，我们回顾了由位于核膜内侧的中间丝核纤层蛋白所决定的细胞核机械响应特性，这些蛋白还会影响转录因子的进入以及更广泛的表观遗传机制。我们总结了响应ECM力学和分子信号组合来调节核纤层蛋白水平和细胞命运决定的信号通路。我们还将讨论最近的研究工作，这些工作突出了核力学在发育、造血分化和癌症转移过程中的微环境锚定和细胞运动中的重要性，同时强调核力学在保护染色质免受应激诱导损伤方面的作用。
