Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing
Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing
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DOI：
10.1038/ncb2370
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发表时间：
2011-12-01
影响因子：
21.3
通讯作者：
Bershadsky, Alexander D.
中科院分区：
文献类型：
--
作者：
Prager-Khoutorsky, Masha;Lichtenstein, Alexandra;Bershadsky, Alexander D.
细胞伸长和极化是对细胞外基质粘附的基本形态发生反应。我们在此证明，人类培养的成纤维细胞在铺在刚性基底上时很容易极化，但不能铺在柔顺基底上。在刚性表面上，形成大且均匀定向的粘着斑，而镀在柔顺基底上的细胞形成许多小的且径向定向的粘连。活细胞监测表明，粘着斑排列先于细胞的整体伸长，表明粘着斑方向可能指导细胞极化。 siRNA 介导的 85 种人类蛋白酪氨酸激酶 (PTK) 敲低诱导细胞极化反应的明显改变，以及细胞牵引力产生和粘着斑形成的不同变化。值得注意的是，刚性依赖性牵引力发展或粘着斑机械传感的变化始终伴随着细胞极化反应的异常。我们提出细胞极化的不同阶段由多个 PTK 依赖性分子检查点调节，这些检查点共同控制细胞收缩性和焦点粘附介导的机械传感。
Cell elongation and polarization are basic morphogenetic responses to extracellular matrix adhesion. We demonstrate here that human cultured fibroblasts readily polarize when plated on rigid, but not on compliant, substrates. On rigid surfaces, large and uniformly oriented focal adhesions are formed, whereas cells plated on compliant substrates form numerous small and radially oriented adhesions. Live-cell monitoring showed that focal adhesion alignment precedes the overall elongation of the cell, indicating that focal adhesion orientation may direct cell polarization. siRNA-mediated knockdown of 85 human protein tyrosine kinases (PTKs) induced distinct alterations in the cell polarization response, as well as diverse changes in cell traction force generation and focal adhesion formation. Remarkably, changes in rigidity-dependent traction force development, or focal adhesion mechanosensing, were consistently accompanied by abnormalities in the cell polarization response. We propose that the different stages of cell polarization are regulated by multiple, PTK-dependent molecular checkpoints that jointly control cell contractility and focal-adhesion-mediated mechanosensing.