University of Mons, Soft Matter & Biomaterials Group, Interfaces and Complex Fluids Laboratory, Research Institute for Biosciences, CIRMAP, Mons, Belgium.
Biology Department, University of Massachusetts Amherst, Amherst, MA, USA.
Nat Rev Mol Cell Biol. 2022 Sep;23(9):583-602. doi: 10.1038/s41580-022-00480-z. Epub 2022 May 5.
As the home of cellular genetic information, the nucleus has a critical role in determining cell fate and function in response to various signals and stimuli. In addition to biochemical inputs, the nucleus is constantly exposed to intrinsic and extrinsic mechanical forces that trigger dynamic changes in nuclear structure and morphology. Emerging data suggest that the physical deformation of the nucleus modulates many cellular and nuclear functions. These functions have long been considered to be downstream of cytoplasmic signalling pathways and dictated by gene expression. In this Review, we discuss an emerging perspective on the mechanoregulation of the nucleus that considers the physical connections from chromatin to nuclear lamina and cytoskeletal filaments as a single mechanical unit. We describe key mechanisms of nuclear deformations in time and space and provide a critical review of the structural and functional adaptive responses of the nucleus to deformations. We then consider the contribution of nuclear deformations to the regulation of important cellular functions, including muscle contraction, cell migration and human disease pathogenesis. Collectively, these emerging insights shed new light on the dynamics of nuclear deformations and their roles in cellular mechanobiology.
细胞核是细胞遗传信息的所在地，在响应各种信号和刺激时，对于决定细胞命运和功能具有关键作用。除了生化输入外，细胞核还不断受到内在和外在机械力的影响，从而引发核结构和形态的动态变化。新出现的数据表明，核的物理变形调节许多细胞和核功能。这些功能长期以来一直被认为是细胞质信号通路的下游，并由基因表达决定。在这篇综述中，我们讨论了细胞核的机械调节的新观点，该观点将从染色质到核纤层和细胞骨架丝的物理连接视为一个单一的机械单元。我们描述了核变形在时间和空间上的关键机制，并对核对变形的结构和功能适应性反应进行了批判性回顾。然后，我们考虑了核变形对调节重要细胞功能（包括肌肉收缩、细胞迁移和人类疾病发病机制）的贡献。总的来说，这些新出现的观点为核变形的动力学及其在细胞机械生物学中的作用提供了新的认识。
