Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nat Cell Biol. 2011 Nov 13;13(12):1457-65. doi: 10.1038/ncb2370.
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.
细胞伸长和极化是细胞对外界基质黏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刚性而非顺应性基底上很容易发生极化。在刚性表面上，形成大而均匀定向的粘着斑，而在顺应性基底上接种的细胞形成许多小而放射状定向的粘着斑。活细胞监测表明，粘着斑的排列先于细胞的整体伸长，表明粘着斑的取向可能指导细胞的极化。siRNA 介导的 85 个人类蛋白酪氨酸激酶 (PTKs) 的敲低导致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多种变化。值得注意的是，与刚性依赖性牵引力发展或粘着斑机械敏感性相关的变化，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受多个依赖于 PTK 的分子检查点调节，这些检查点共同控制细胞收缩性和粘着斑介导的机械敏感性。
