The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments.
The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments.
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DOI：
10.1126/sciadv.abd4058
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Chaudhuri O
中科院分区：
文献类型：
--
作者：
Lee HP;Alisafaei F;Adebawale K;Chang J;Shenoy VB;Chaudhuri O
细胞利用核活塞在限制矩阵中机械地产生迁移路径。当迁移路径预先存在且具有弹性时，细胞在受限微环境中的迁移受到硬核通过毛孔变形的能力的限制，但细胞如何生成这些路径仍不清楚。在这里，我们揭示了核在受限微环境中机械地为间充质干细胞(MSCs)生成迁移路径的机制。骨髓间充质干细胞在粘弹性和可塑性的纳米孔洞限制水凝胶中迁移，但在弹性更大的水凝胶中不迁移。为了迁移，MSCs首先延长薄薄的突起，这些突起因核活塞而随着时间的推移而变宽，从而在限制基质中开辟了一条迁移路径。理论模拟和实验表明，核进入突起激活了机械敏感离子通道，导致离子流入增加渗透压，从而胜过静水压力来驱动突起膨胀。因此，核心不是限制迁移，而是通过生成迁移路径来支持迁移。
Cells utilize a nuclear piston to mechanically generate migration paths in confining matrices. Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths.
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影响因子：
16.6
作者：
Infante E;Castagnino A;Ferrari R;Monteiro P;Agüera-González S;Paul-Gilloteaux P;Domingues MJ;Maiuri P;Raab M;Shanahan CM;Baffet A;Piel M;Gomes ER;Chavrier P
通讯作者：
Chavrier P
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
3.5
作者：
Jones, M. B.;Fulford, G. R.;Collins, M. J.
通讯作者：
Collins, M. J.
影响因子：
5.5
作者：
Carey, Shawn P.;Rahman, Aniqua;Reinhart-King, Cynthia A.
通讯作者：
Reinhart-King, Cynthia A.
DOI：
10.1007/s00249-016-1173-7
发表时间：
2016-10
影响因子：
2
作者：
Iamshanova, Oksana;Mariot, Pascal;Lehen'kyi, V'yacheslav;Prevarskaya, Natalia
通讯作者：
Prevarskaya, Natalia