Institute for Molecular Bioscience, Genomics of Development and Disease division, The University of Queensland, 306 Carmody Road, St Lucia, 4072, QLD, Australia.
Institute for Molecular Bioscience, Cell Biology and Molecular Medicine division, The University of Queensland, 306 Carmody Road, St Lucia, 4072, QLD, Australia.
Nat Commun. 2017 Nov 10;8(1):1402. doi: 10.1038/s41467-017-01325-6.
Forces play diverse roles in vascular development, homeostasis and disease. VE-cadherin at endothelial cell-cell junctions links the contractile acto-myosin cytoskeletons of adjacent cells, serving as a tension-transducer. To explore tensile changes across VE-cadherin in live zebrafish, we tailored an optical biosensor approach, originally established in vitro. We validate localization and function of a VE-cadherin tension sensor (TS) in vivo. Changes in tension across VE-cadherin observed using ratio-metric or lifetime FRET measurements reflect acto-myosin contractility within endothelial cells. Furthermore, we apply the TS to reveal biologically relevant changes in VE-cadherin tension that occur as the dorsal aorta matures and upon genetic and chemical perturbations during embryonic development.
力在血管发育、稳态和疾病中发挥多种作用。内皮细胞-细胞连接处的血管内皮钙黏蛋白将相邻细胞的收缩性肌动球蛋白细胞骨架连接起来,充当张力传感器。为了在活体斑马鱼中探索跨血管内皮钙黏蛋白的拉伸变化,我们对最初在体外建立的光学生物传感器方法进行了定制。我们在体内验证了血管内皮钙黏蛋白张力传感器 (TS) 的定位和功能。使用比率或寿命 FRET 测量观察到的跨血管内皮钙黏蛋白的张力变化反映了内皮细胞内的肌动球蛋白收缩性。此外,我们应用 TS 来揭示在背主动脉成熟过程中以及在胚胎发育过程中遗传和化学干扰时发生的与生物学相关的血管内皮钙黏蛋白张力变化。