Dorsoventral polarity directs cell responses to migration track geometries
Dorsoventral polarity directs cell responses to migration track geometries
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DOI：
10.1126/sciadv.aba6505
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发表时间：
2020-07-01
期刊：
影响因子：
13.6
通讯作者：
Konstantopoulos, Konstantinos
中科院分区：
文献类型：
--
作者：
Wisniewski, Emily O.;Mistriotis, Panagiotis;Konstantopoulos, Konstantinos
迁移细胞如何以不同的方式适应和响应细胞外轨迹几何形状仍然未知。通过活体成像，我们证明了入侵细胞在体内表现出背腹侧（从上到下）极性。为了研究背腹侧极性对不同围合几何形状的细胞运动的影响，我们制作了固定横截面积的微通道，尽管具有不同的宽高比。沿背腹侧极性轴施加的垂直限制可诱导肌球蛋白ii依赖的核硬化，从而导致细胞两极的RhoA过度激活和基于气泡的缓慢迁移。在侧向约束下，垂直于背腹侧极性轴，核周肌球蛋白II的缺失不能增加核刚度。因此，细胞维持基本的RhoA活性并显示更快的间质迁移。总之，通过集成微加工、成像技术和活体显微镜，我们证明了在体内和体外观察到的背腹侧极性，通过空间调节RhoA活性来指导禁闭条件下的细胞反应，从而控制基于泡的和间质的迁移。
How migrating cells differentially adapt and respond to extracellular track geometries remains unknown. Using intravital imaging, we demonstrate that invading cells exhibit dorsoventral (top-to-bottom) polarity in vivo. To investigate the impact of dorsoventral polarity on cell locomotion through different confining geometries, we fabricated microchannels of fixed cross-sectional area, albeit with distinct aspect ratios. Vertical confinement, exerted along the dorsoventral polarity axis, induces myosin II-dependent nuclear stiffening, which results in RhoA hyperactivation at the cell poles and slow bleb-based migration. In lateral confinement, directed perpendicularly to the dorsoventral polarity axis, the absence of perinuclear myosin II fails to increase nuclear stiffness. Hence, cells maintain basal RhoA activity and display faster mesenchymal migration. In summary, by integrating microfabrication, imaging techniques, and intravital microscopy, we demonstrate that dorsoventral polarity, observed in vivo and in vitro, directs cell responses in confinement by spatially tuning RhoA activity, which controls bleb-based versus mesenchymal migration.