Nuclear deformability constitutes a rate-limiting step during cell migration in 3-D environments.
Nuclear deformability constitutes a rate-limiting step during cell migration in 3-D environments.
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DOI：
10.1007/s12195-014-0342-y
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发表时间：
2014-09-01
影响因子：
2.8
通讯作者：
Lammerding, Jan
中科院分区：
文献类型：
--
作者：
Davidson, Patricia M.;Denais, Celine;Bakshi, Maya C.;Lammerding, Jan
细胞运动在许多生理和病理环境中起着关键作用，从伤口愈合到癌症转移。虽然细胞在二维（2-D）基质上的迁移已经研究了几十年，但细胞在3-D环境中移动时所面临的物理挑战现在才出现。特别是，细胞核占据了细胞体积的大部分，通常比周围的细胞质硬得多，当细胞遇到间隙空间、细胞外基质或小毛细血管中的狭窄收缩时，细胞核可能会造成主要障碍。使用新的微流体装置，允许观察细胞以高空间和时间分辨率移动通过精确定义的几何形状，我们确定核变形能力作为细胞通过小于细胞核大小的收缩的能力的关键因素。此外，我们发现，细胞的核膜蛋白核纤层蛋白A/C，这是核硬度的主要决定因素的水平降低，通过显着更快地通过狭窄的收缩在主动迁移和被动灌注。鉴于最近的报道，许多人类癌症改变了核纤层蛋白的表达，我们的研究结果表明，一种新的生物物理机制，核结构和组成的变化可能会促进癌细胞的侵袭和转移。
Cell motility plays a critical role in many physiological and pathological settings, ranging from wound healing to cancer metastasis. While cell migration on 2-dimensional (2-D) substrates has been studied for decades, the physical challenges cells face when moving in 3-D environments are only now emerging. In particular, the cell nucleus, which occupies a large fraction of the cell volume and is normally substantially stiffer than the surrounding cytoplasm, may impose a major obstacle when cells encounter narrow constrictions in the interstitial space, the extracellular matrix, or small capillaries. Using novel microfluidic devices that allow observation of cells moving through precisely defined geometries at high spatial and temporal resolution, we determined nuclear deformability as a critical factor in the cells’ ability to pass through constrictions smaller than the size of the nucleus. Furthermore, we found that cells with reduced levels of the nuclear envelope proteins lamins A/C, which are the main determinants of nuclear stiffness, passed significantly faster through narrow constrictions during active migration and passive perfusion. Given recent reports that many human cancers have altered lamin expression, our findings suggest a novel biophysical mechanism by which changes in nuclear structure and composition may promote cancer cell invasion and metastasis.
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影响因子：
3.4
作者：
Hale, Christopher M.;Shrestha, Arun L.;Wirtz, Denis
通讯作者：
Wirtz, Denis
影响因子：
4.8
作者：
Balzer, Eric M.;Tong, Ziqiu;Konstantopoulos, Konstantinos
通讯作者：
Konstantopoulos, Konstantinos
影响因子：
--
作者：
Isermann, Philipp;Davidson, Patricia M;Sliz, Josiah D;Lammerding, Jan
通讯作者：
Lammerding, Jan
DOI：
10.1073/pnas.0702576104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Pajerowski, J. David;Dahl, Kris Noel;Discher, Dennis E.
通讯作者：
Discher, Dennis E.
影响因子：
3.4
作者：
Lee, Jerry S. H.;Hale, Christopher M.;Wirtz, Denis
通讯作者：
Wirtz, Denis