Fine control of nuclear confinement identifies a threshold deformation leading to lamina rupture and induction of specific genes
Fine control of nuclear confinement identifies a threshold deformation leading to lamina rupture and induction of specific genes
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DOI：
10.1039/c2ib20056b
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发表时间：
2012-11-01
影响因子：
2.5
通讯作者：
Piel, Matthieu
中科院分区：
文献类型：
--
作者：
Le Berre, Mael;Aubertin, Johannes;Piel, Matthieu
寻求了解细胞的机械和几何环境如何影响其行为和命运一直是推动细胞生物学研究新技术发展的主要力量。尽管该领域取得了快速进展，但为了弥合经典和简单的细胞培养板与实际组织的生物学现实之间的差距，仍然存在许多挑战。在组织中，细胞的物理空间受到邻近细胞和细胞外基质的限制。在这里，我们提出了一种简单且多功能的设备来精确动态地控制培养细胞中的这种限制参数。我们发现存在一个精确的阈值变形，超过该阈值核纤层就会破裂并重建，而核体积会发生变化。我们还表明，不同的核变形与特定基因组的表达相关，包括核因子和经典的机械转导途径。因此，这种多功能装置能够通过限制和相关分子事件的相关研究来精确控制细胞和核变形。
The quest to understand how the mechanical and geometrical environment of cells impacts their behavior and fate has been a major force driving the recent development of new technologies in cell biology research. Despite rapid advances in this field, many challenges remain in order to bridge the gap between the classical and simple cell culture plate and the biological reality of actual tissue. In tissues, cells have their physical space constrained by neighboring cells and the extracellular matrix. Here, we propose a simple and versatile device to precisely and dynamically control this confinement parameter in cultured cells. We show that there is a precise threshold deformation above which the nuclear lamina breaks and reconstructs, whereas nuclear volume changes. We also show that different nuclear deformations correlate with the expression of specific sets of genes, including nuclear factors and classical mechanotransduction pathways. This versatile device thus enables the precise control of cell and nuclear deformation by confinement and the correlative study of the associated molecular events.