Extracellular rigidity sensing by talin isoform-specific mechanical linkages.
Extracellular rigidity sensing by talin isoform-specific mechanical linkages.
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DOI：
10.1038/ncb3268
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发表时间：
2015-12
影响因子：
21.3
通讯作者：
Grashoff C
中科院分区：
文献类型：
--
作者：
Austen K;Ringer P;Mehlich A;Chrostek-Grashoff A;Kluger C;Klingner C;Sabass B;Zent R;Rief M;Grashoff C
细胞粘附和感知组织硬度差异的能力对于器官发育和功能至关重要。然而，粘附细胞检测细胞外基质顺应性的中心机制仍然未知。使用两个单分子校准的生物传感器，允许以前无法访问的，但在细胞中的生理高度相关的力制度的分析，我们证明了整合素激活剂塔林建立细胞粘附，这是必不可少的细胞探测组织刚度的机械联系。Talin键暴露于一系列皮牛顿（pN）力，并且在细胞粘附期间平均承受7-10 pN，这取决于它们与f-肌动蛋白和黏着斑蛋白的缔合。破坏塔林的机械接合不损害整合素激活和初始细胞粘附，但防止局灶性粘附增强，从而细胞外刚性传感。有趣的是，talin力学是异构体特异性的，因此talin-1或talin-2的表达调节细胞外刚性传感。
The ability of cells to adhere and sense differences in tissue stiffness is crucial for organ development and function. The central mechanisms by which adherent cells detect extracellular matrix compliance, however, are still unknown. Using two single-molecule–calibrated biosensors that allow the analysis of a previously inaccessible but physiologically highly relevant force regime in cells, we demonstrate that the integrin activator talin establishes mechanical linkages upon cell adhesion, which are indispensable for cells to probe tissue stiffness. Talin linkages are exposed to a range of piconewton (pN) forces and bear, on average, 7–10 pN during cell adhesion depending on their association with f-actin and vinculin. Disruption of talin’s mechanical engagement does not impair integrin activation and initial cell adhesion but prevents focal adhesion reinforcement and thus extracellular rigidity sensing. Intriguingly, talin mechanics are isoform-specific so that expression of either talin-1 or talin-2 modulates extracellular rigidity sensing.