Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent
Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent
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DOI：
10.3390/cells8050427
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发表时间：
2019-05-01
期刊：
影响因子：
6
通讯作者：
Stroka, Kimberly M.
中科院分区：
文献类型：
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作者：
Doolin, Mary T.;Ornstein, Thea S.;Stroka, Kimberly M.
细胞对机械微环境的机械感测调节细胞表型和功能。细胞核在机械传感中至关重要，因为它将外力从细胞微环境传递到容纳染色质的核膜。本研究旨在阐明机械约束如何影响几种细胞类型内的核变形，并确定细胞骨架元素在控制核变形中的作用。将人癌细胞（MDA-MB-231）、人间充质干细胞（MSC）和小鼠成纤维细胞（L929）接种在含有不同横截面积的微通道的聚二甲基硅氧烷（PDMS）微流体装置内，并通过荧光细胞核的图像处理来定量核形态和体积。我们发现，在MSC和MDA-MB-231细胞中，核长轴长度随着限制的增加而保持相当恒定，但在L929细胞中随着限制的增加而增加。L929细胞和MSCs的核体积在最狭窄的通道中减少。然而，L929细胞核在无限制通道中比MSC细胞核各向同性得多。当微管聚合或肌球蛋白II的收缩性被抑制，核变形仅在宽通道中的MSC中改变。这项工作通知我们的理解核力学在生理相关的空间，并建议不同的作用，调节核变形的细胞骨架在不同的细胞类型。
Mechanosensing of the mechanical microenvironment by cells regulates cell phenotype and function. The nucleus is critical in mechanosensing, as it transmits external forces from the cellular microenvironment to the nuclear envelope housing chromatin. This study aims to elucidate how mechanical confinement affects nuclear deformation within several cell types, and to determine the role of cytoskeletal elements in controlling nuclear deformation. Human cancer cells (MDA-MB-231), human mesenchymal stem cells (MSCs), and mouse fibroblasts (L929) were seeded within polydimethylsiloxane (PDMS) microfluidic devices containing microchannels of varying cross-sectional areas, and nuclear morphology and volume were quantified via image processing of fluorescent cell nuclei. We found that the nuclear major axis length remained fairly constant with increasing confinement in MSCs and MDA-MB-231 cells, but increased with increasing confinement in L929 cells. Nuclear volume of L929 cells and MSCs decreased in the most confining channels. However, L929 nuclei were much more isotropic in unconfined channels than MSC nuclei. When microtubule polymerization or myosin II contractility was inhibited, nuclear deformation was altered only in MSCs in wide channels. This work informs our understanding of nuclear mechanics in physiologically relevant spaces, and suggests diverging roles of the cytoskeleton in regulating nuclear deformation in different cell types.