Extracellular Forces Cause the Nucleus to Deform in a Highly Controlled Anisotropic Manner.
Extracellular Forces Cause the Nucleus to Deform in a Highly Controlled Anisotropic Manner.
复制标题
DOI：
10.1038/srep21300
复制
发表时间：
2016-02-19
影响因子：
4.6
通讯作者：
Pelling AE
中科院分区：
文献类型：
--
作者：
Haase K;Macadangdang JK;Edrington CH;Cuerrier CM;Hadjiantoniou S;Harden JL;Skerjanc IS;Pelling AE
在细胞外环境中产生的物理力对细胞命运和基因调控具有深远的影响;然而，控制这种敏感性的潜在生物物理机制仍然难以捉摸。据推测，基因表达可能受到细胞核对力的反应的物理变形的影响。在这里，使用3 T3 s作为模型，我们证明，细胞外力导致细胞核快速变形（<1秒）优先沿着其较短的核轴，在各向异性的方式。核各向异性被证明是由完整细胞内的细胞骨架，与肌动蛋白和微管抵抗正交应变。重要的是，核的各向异性是内在的，并且在孤立的核中观察到。这种行为的敏感性受到染色质组织和层粘连蛋白A表达的影响。对力的各向异性反应在来自分化和未分化细胞类型的检查的细胞核的阵列中也是高度保守的。虽然这种保守的物质特性的功能目的仍然难以捉摸，但它可能提供了一种机制，通过这种机制，微环境中的机械线索被迅速传递到基因组。
Physical forces arising in the extra-cellular environment have a profound impact on cell fate and gene regulation; however the underlying biophysical mechanisms that control this sensitivity remain elusive. It is hypothesized that gene expression may be influenced by the physical deformation of the nucleus in response to force. Here, using 3T3s as a model, we demonstrate that extra-cellular forces cause cell nuclei to rapidly deform (<1 s) preferentially along their shorter nuclear axis, in an anisotropic manner. Nuclear anisotropy is shown to be regulated by the cytoskeleton within intact cells, with actin and microtubules resistant to orthonormal strains. Importantly, nuclear anisotropy is intrinsic, and observed in isolated nuclei. The sensitivity of this behaviour is influenced by chromatin organization and lamin-A expression. An anisotropic response to force was also highly conserved amongst an array of examined nuclei from differentiated and undifferentiated cell types. Although the functional purpose of this conserved material property remains elusive, it may provide a mechanism through which mechanical cues in the microenvironment are rapidly transmitted to the genome.