Focal adhesion size uniquely predicts cell migration
Focal adhesion size uniquely predicts cell migration
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DOI：
10.1096/fj.12-220160
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发表时间：
2013-04-01
期刊：
影响因子：
4.8
通讯作者：
Wirtz, Denis
中科院分区：
文献类型：
--
作者：
Kim, Dong-Hwee;Wirtz, Denis
局灶性粘连是在细胞基底表面组织的大蛋白复合物，其将细胞外基质与细胞骨架物理连接，并且长期以来一直被推测介导细胞迁移。然而，这些蛋白质调节细胞运动性是否真的需要这些分子组分聚集成粘着斑尚不清楚。在这里，我们使用定量显微镜来表征描述符的粘着斑和细胞运动的小鼠胚胎成纤维细胞和人纤维肉瘤细胞，在广泛的基质的依从性和以下的遗传操作的粘着斑蛋白（黏着斑蛋白，塔林蛋白，zyxin，FAK，和paxilin）。该分析揭示了局灶性粘连的平均大小（而不是它们的数量、表面密度或形状）与细胞速度之间的紧密的双相高斯关系。这种关系的预测能力通过破坏非焦点粘附蛋白（α-辅肌动蛋白，F-肌动蛋白和肌球蛋白II）和亚细胞器（线粒体，核DNA等）得到全面验证。目前尚不清楚其是否影响粘着斑或细胞迁移。这项研究表明，粘着斑的平均大小稳健而精确地预测了细胞速度，而与粘着斑表面密度和分子组成无关。金，D.- H、维尔茨，D.粘着斑大小唯一地预测细胞迁移。FASEB J.27，1351-1361（2013）。www.fasebj.org
Focal adhesions are large protein complexes organized at the basal surface of cells, which physically connect the extracellular matrix to the cytoskeleton and have long been speculated to mediate cell migration. However, whether clustering of these molecular components into focal adhesions is actually required for these proteins to regulate cell motility is unclear. Here we use quantitative microscopy to characterize descriptors of focal adhesion and cell motility for mouse embryonic fibroblasts and human fibrosarcoma cells, across a wide range of matrix compliance and following genetic manipulations of focal adhesion proteins (vinculin, talin, zyxin, FAK, and paxilin). This analysis reveals a tight, biphasic gaussian relationship between mean size of focal adhesions (not their number, surface density, or shape) and cell speed. The predictive power of this relationship is comprehensively validated by disrupting nonfocal adhesion proteins (alpha-actinin, F-actin, and myosin II) and subcellular organelles (mitochondria, nuclear DNA, etc.) not known to affect either focal adhesions or cell migration. This study suggests that the mean size of focal adhesions robustly and precisely predicts cell speed independently of focal adhesion surface density and molecular composition.-Kim, D.-H., Wirtz, D. Focal adhesion size uniquely predicts cell migration. FASEB J. 27, 1351-1361 (2013). www.fasebj.org