Vinculin transmits high-level integrin tensions that are dispensable for focal adhesion formation

Vinculin transmits high-level integrin tensions that are dispensable for focal adhesion formation
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DOI:
10.1016/j.bpj.2022.11.013
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发表时间:
2023-01-03
影响因子:
3.4
通讯作者:
Wang, Xuefeng
Wang, Xuefeng
中科院分区:
生物学3区
文献类型:
--
作者:
Austin, Jacob;Tu, Ying;Wang, Xuefeng

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粘着斑(FAs)传递力并介导细胞和基质之间的机械转导。以往的研究表明,整合素传递力是调节FA形成的关键。由于黏着斑蛋白是一个重要的FA蛋白参与整合素张力传递,这项工作研究之间的关系整合素张力(力),黏着斑蛋白(蛋白质),和FA形成(结构)的整合素张力操纵,力可视化和黏着斑蛋白敲除(KO)。采用两种基于DNA的整合素张力工具:张力计系绳(TGT)和集成张力传感器(ITS),TGT将整合素张力限制在设计的Ttol(张力公差)值以下,ITS通过荧光可视化整合素张力高于Ttol值。结果表明,在Ttol为54 pN的TGT表面上形成了大的FA(面积>1 mm 2),但在Ttol值较低的TGT表面上没有形成。FA形成的时间序列分析表明,焦点复合物(面积
Focal adhesions (FAs) transmit force and mediate mechanotransduction between cells and the matrix. Previous studies revealed that integrin-transmitted force is critical to regulate FA formation. As vinculin is a prominent FA protein implicated in integrin tension transmission, this work studies the relation among integrin tensions (force), vinculin (protein), and FA formation (structure) by integrin tension manipulation, force visualization and vinculin knockout (KO). Two DNA-based integrin tension tools are adopted: tension gauge tether (TGT) and integrative tension sensor (ITS), with TGT restricting integrin tensions under a designed Ttol (tension tolerance) value and ITS visualizing integrin tensions above the Ttol value by fluorescence. Results show that large FAs (area >1 mm2) were formed on the TGT surface with Ttol of 54 pN but not on those with lower Ttol values. Time-series analysis of FA formation shows that focal complexes (area