The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells.
The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells.
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DOI：
10.3390/cells7070066
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发表时间：
2018-06-26
期刊：
影响因子：
6
通讯作者：
Conway DE
中科院分区：
文献类型：
--
作者：
Baddam SR;Arsenovic PT;Narayanan V;Duggan NR;Mayer CR;Newman ST;Abutaleb DA;Mohan A;Kowalczyk AP;Conway DE
细胞-细胞连接是许多组织中的关键结构，用于将细胞机械耦合在一起，细胞间的信号传递，以及建立屏障。在许多组织中，桥粒是细胞-细胞连接的重要组成部分。桥粒丢失或损伤在心脏和皮肤分别表现为心律失常和皮肤水泡的临床表型。因为心脏和皮肤是承受很大机械应力的组织，我们假设桥粒，类似于粘连连接，也会经历显著的拉伸负荷。为了直接测量跨越桥粒的机械力，我们利用现有的TSmod Förster共振能量转移(FRET)力生物传感器开发并验证了桥粒蛋白-2(DSG-2)力传感器。当在人心肌细胞中表达时，力传感器报告了DSG-2在收缩过程中的高拉伸负荷。此外，当表达在Madin-Darby犬肾(MDCK)上皮或表皮(A431)单层时，传感器还报告了拉伸载荷。最后，我们观察到，与2D单层相比，3D MDCK腺泡中的DSG-2力更高。综上所述，我们的结果表明，桥粒在静息细胞中经历低水平的机械张力，而在主动加载过程中的力明显较大。
Cell-cell junctions are critical structures in a number of tissues for mechanically coupling cells together, cell-to-cell signaling, and establishing a barrier. In many tissues, desmosomes are an important component of cell-cell junctions. Loss or impairment of desmosomes presents with clinical phenotypes in the heart and skin as cardiac arrhythmias and skin blistering, respectively. Because heart and skin are tissues that are subject to large mechanical stresses, we hypothesized that desmosomes, similar to adherens junctions, would also experience significant tensile loading. To directly measure mechanical forces across desmosomes, we developed and validated a desmoglein-2 (DSG-2) force sensor, using the existing TSmod Förster resonance energy transfer (FRET) force biosensor. When expressed in human cardiomyocytes, the force sensor reported high tensile loading of DSG-2 during contraction. Additionally, when expressed in Madin-Darby canine kidney (MDCK) epithelial or epidermal (A431) monolayers, the sensor also reported tensile loading. Finally, we observed higher DSG-2 forces in 3D MDCK acini when compared to 2D monolayers. Taken together, our results show that desmosomes experience low levels of mechanical tension in resting cells, with significantly higher forces during active loading.
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DOI：
10.1073/pnas.1701703114
发表时间：
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影响因子：
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