Focal adhesion displacement magnitude is a unifying feature of tensional homeostasis
Focal adhesion displacement magnitude is a unifying feature of tensional homeostasis
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焦点粘附位移大小是张力稳态的统一特征
DOI：
10.1016/j.actbio.2020.06.043
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发表时间：
2020
影响因子：
9.7
通讯作者：
Smith, Michael L.
中科院分区：
文献类型：
--
作者：
Xu, Han;Donegan, Stephanie;Dreher, Jordan M.;Stark, Alicia J.;Canović, Elizabeth P.;Stamenović, Dimitrije;Smith, Michael L.
人们普遍认为在器官和组织的长度尺度上存在张力稳态，但细胞长度尺度上张力调节的机制尚不清楚。在这项研究中，我们探讨了张力稳态是否来自于单个局灶黏附（FA）的行为，FA是一种将细胞应力传递给周围细胞外基质的亚细胞结构。过去的研究表明，细胞的收缩性直到达到一定的位移才能建立，因此我们假设张力稳态可能需要一个底物位移的阈值水平。采用微纹牵引显微镜研究了牛血管平滑肌细胞和牛主动脉内皮细胞在刚度为3.6、6.7、13.6和30 kPa的基质上产生的FA牵引力。这里观察到的FA动力学最显著的特征是，由FA牵引力引起的基底位移是决定FA张拉稳定性的统一特征。当衬底位移超过约1 μm时，无论细胞类型或衬底刚度如何，FAs都表现出牵引力的时间波动急剧下降。这些发现使我们得出结论，牵引力动力学共同决定细胞或细胞群是否发展张力内平衡，这一见解对于充分理解健康条件下基质刚度如何影响细胞行为是必要的，更重要的是，在癌症或血管老化等病理条件下，环境刚度被改变。张力稳态被广泛认为存在于器官和组织的长度尺度上，但细胞长度尺度上张力调节的机制尚不清楚。在这项研究中，我们探讨了张力稳态是否来自于单个局灶黏附（FA）的行为，FA是一种将细胞应力传递到细胞外基质的亚细胞结构。我们利用微纹牵引显微镜测量血管平滑肌细胞和内皮细胞中FA力的时间间隔。我们发现，基底位移的大小决定了FA是否具有低牵引力的时间变异性。这一发现意义重大，因为它是第一个已知的张力稳态特征，它在一系列环境条件和细胞类型中广泛统一。
Tensional homeostasis is widely recognized to exist at the length scales of organs and tissues, but the cellular length scale mechanism for tension regulation is not known. In this study, we explored whether tensional homeostasis emerges from the behavior of the individual focal adhesion (FA), which is the subcellular structure that transmits cell stress to the surrounding extracellular matrix. Past studies have suggested that cell contractility builds up until a certain displacement is achieved, and we thus hypothesized that tensional homeostasis may require a threshold level of substrate displacement. Micropattern traction microscopy was used to study a wide range of FA traction forces generated by bovine vascular smooth muscle cells and bovine aortic endothelial cells cultured on substrates of stiffness of 3.6, 6.7, 13.6, and 30 kPa. The most striking feature of FA dynamics observed here is that the substrate displacement resulting from FA traction forces is a unifying feature that determines FA tensional stability. Beyond approximately 1 μm of substrate displacement, FAs, regardless of cell type or substrate stiffness, exhibit a precipitous drop in temporal fluctuations of traction forces. These findings lead us to the conclusion that traction force dynamics collectively determine whether cells or cell ensembles develop tensional homeostasis, and this insight is necessary to fully understand how matrix stiffness impacts cellular behavior in healthy conditions and, more important, in pathological conditions such as cancer or vascular aging, where environmental stiffness is altered.Statement of SignificanceTensional homeostasis is widely recognized to exist at the length scales of organs and tissues, but the cellular length scale mechanism for tension regulation is not known. In this study, we explored whether tensional homeostasis emerges from the behavior of the individual focal adhesion (FA), which is the subcellular structure that transmits cell stress to the extracellular matrix. We utilized micropattern traction microscopy to measure time-lapses of FA forces in vascular smooth muscle cells and in endothelial cells. We discovered that the magnitude of the substrate displacement determines whether the FA has low temporal variability of traction forces. This finding is significant since it is the first known feature of tensional homeostasis that is broadly unifying across a range of environmental conditions and cell types.