Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction
Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction
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DOI：
10.1073/pnas.1612208113
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发表时间：
2016-12-20
影响因子：
11.1
通讯作者：
Nelson, W. James
中科院分区：
文献类型：
--
作者：
Cohen, Daniel J.;Gloerich, Martijn;Nelson, W. James
上皮单分子层在受伤时可以自我修复。在愈合过程中，细胞集体迁移到伤口部位，聚集的组织前沿碰撞并形成稳定的界面。为了愈合，迁移组织必须形成细胞间的黏附，并从细胞迁移的前后极性特征重新组织到上皮的顶基极性。然而，确定诱导碰撞组织停止迁移和愈合的“停止信号”仍然是一个悬而未决的问题。上皮细胞与基底细胞外基质（ECM）形成基于整合素的粘附，并在细胞间的正交侧表面形成e -钙粘蛋白介导的细胞粘附。目前的生物工具还无法探测这种多细胞三维界面来确定停止信号。我们通过开发一种独特的生物界面来模拟上皮细胞粘附的3D组织来解决这个问题。这种“最小组织模拟物”（MTM）由基础ECM底物和覆盖有纯化的e -钙粘蛋白细胞外结构域的垂直表面组成，设计用于与上皮单层愈合边缘碰撞。三维成像显示，细胞之间形成了粘附，e-钙粘蛋白包被的MTM类似于天然上皮细胞-细胞连接的形态和动力学，并诱导了上皮细胞自愈过程中发生的相同极性转变。这些结果表明，在适当的3D环境中，e -钙粘蛋白构成了诱导自我修复的最小必要停止信号。Ecad: Fc MTM稳定地整合到上皮组织中，并减少了界面上的迁移，这表明这种生物界面是现有组织-材料界面的补充方法。
Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell-cell adhesions and reorganize from the front-rear polarity characteristic of cell migration to the apical-basal polarity of an epithelium. However, identifying the "stop signal" that induces colliding tissues to cease migrating and heal remains an open question. Epithelial cells form integrin-based adhesions to the basal extracellular matrix (ECM) and E-cadherin-mediated cell-cell adhesions on the orthogonal, lateral surfaces between cells. Current biological tools have been unable to probe this multicellular 3D interface to determine the stop signal. We addressed this problem by developing a unique biointerface that mimicked the 3D organization of epithelial cell adhesions. This "minimal tissue mimic" (MTM) comprised a basal ECM substrate and a vertical surface coated with purified extracellular domain of E-cadherin, and was designed for collision with the healing edge of an epithelial monolayer. Three-dimensional imaging showed that adhesions formed between cells, and the E-cadherin-coated MTM resembled the morphology and dynamics of native epithelial cell-cell junctions and induced the same polarity transition that occurs during epithelial self-healing. These results indicate that E-cadherin presented in the proper 3D context constitutes a minimum essential stop signal to induce self-healing. That the Ecad: Fc MTM stably integrated into an epithelial tissue and reduced migration at the interface suggests that this biointerface is a complimentary approach to existing tissue-material interfaces.