An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells.,Nature Communications

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An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-24 , DOI: 10.1038/s41467-020-14390-1
Dirk Ollech _{1,

2,

3} , Tim Pflästerer _{1,

2,

4} , Adam Shellard ₅ , Chiara Zambarda _{1,

2} , Joachim Pius Spatz _{1,

2} , Philippe Marcq ₆ , Roberto Mayor ₅ , Richard Wombacher ₄ , Elisabetta Ada Cavalcanti-Adam _{1,

2}

Affiliation

The cadherin-catenin complex at adherens junctions (AJs) is essential for the formation of cell-cell adhesion and epithelium integrity; however, studying the dynamic regulation of AJs at high spatio-temporal resolution remains challenging. Here we present an optochemical tool which allows reconstitution of AJs by chemical dimerization of the force bearing structures and their precise light-induced dissociation. For the dimerization, we reconstitute acto-myosin connection of a tailless E-cadherin by two ways: direct recruitment of α-catenin, and linking its cytosolic tail to the transmembrane domain. Our approach enables a specific ON-OFF switch for mechanical coupling between cells that can be controlled spatially on subcellular or tissue scale via photocleavage. The combination with cell migration analysis and traction force microscopy shows a wide-range of applicability and confirms the mechanical contribution of the reconstituted AJs. Remarkably, in vivo our tool is able to control structural and functional integrity of the epidermal layer in developing Xenopus embryos.

中文翻译：

一种光化学工具，用于光诱导粘附连接解离，以控制细胞之间的机械耦合。

粘附连接 (AJ) 处的钙粘蛋白-连环蛋白复合物对于细胞间粘附和上皮完整性的形成至关重要；然而，在高时空分辨率下研究 AJ 的动态调节仍然具有挑战性。在这里，我们提出了一种光化学工具，它允许通过受力结构的化学二聚化及其精确的光诱导解离来重建 AJ。对于二聚化，我们通过两种方式重建无尾 E-钙粘蛋白的肌动球蛋白连接：直接招募 α-连环蛋白，并将其胞质尾部连接到跨膜结构域。我们的方法实现了细胞之间机械耦合的特定开关，可以通过光裂解在亚细胞或组织尺度上进行空间控制。与细胞迁移分析和牵引力显微镜的结合显示出广泛的适用性，并证实了重组 AJ 的机械贡献。值得注意的是，在体内，我们的工具能够控制爪蟾胚胎发育中表皮层的结构和功能完整性。

更新日期：2020-01-24

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