McGregor Alexandra Lynn, Hsia Chieh-Ren, Lammerding Jan
Nancy C. and Peter E. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Curr Opin Cell Biol. 2016 Jun;40:32-40. doi: 10.1016/j.ceb.2016.01.011. Epub 2016 Feb 16.
From embryonic development to cancer metastasis, cell migration plays a central role in health and disease. It is increasingly becoming apparent that cells migrating in three-dimensional (3-D) environments exhibit some striking differences compared with their well-established 2-D counterparts. One key finding is the significant role the nucleus plays during 3-D migration: when cells move in confined spaces, the cell body and nucleus must deform to squeeze through available spaces, and the deformability of the large and relatively rigid nucleus can become rate-limiting. In this review, we highlight recent findings regarding the role of nuclear mechanics in 3-D migration, including factors that govern nuclear deformability, and emerging mechanisms by which cells apply cytoskeletal forces to the nucleus to facilitate nuclear translocation. Intriguingly, the 'physical barrier' imposed by the nucleus also impacts cytoplasmic dynamics that affect cell migration and signaling, and changes in nuclear structure resulting from the mechanical forces acting on the nucleus during 3-D migration could further alter cellular function. These findings have broad relevance to the migration of both normal and cancerous cells inside living tissues, and motivate further research into the molecular details by which cells move their nuclei, as well as the consequences of the mechanical stress on the nucleus.
从胚胎发育到癌症转移，细胞迁移在健康与疾病过程中都起着核心作用。越来越明显的是，与在二维（2-D）环境中迁移的细胞相比，在三维（3-D）环境中迁移的细胞表现出一些显著差异。一个关键发现是细胞核在三维迁移过程中发挥的重要作用：当细胞在受限空间中移动时，细胞体和细胞核必须变形才能挤过可用空间，而相对较大且刚性的细胞核的可变形性可能成为限速因素。在这篇综述中，我们重点介绍了关于核力学在三维迁移中的作用的最新发现，包括控制细胞核可变形性的因素，以及细胞将细胞骨架力施加于细胞核以促进核转位的新机制。有趣的是，细胞核形成的“物理屏障”也会影响影响细胞迁移和信号传导的细胞质动力学，并且在三维迁移过程中作用于细胞核的机械力导致的核结构变化可能会进一步改变细胞功能。这些发现与活组织内正常细胞和癌细胞的迁移都密切相关，并促使人们进一步研究细胞移动细胞核的分子细节，以及机械应力对细胞核的影响。
