Spatial organization of the extracellular matrix regulates cell-cell junction positioning
Spatial organization of the extracellular matrix regulates cell-cell junction positioning
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DOI：
10.1073/pnas.1106377109
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发表时间：
2012-01-31
影响因子：
11.1
通讯作者：
Thery, Manuel
中科院分区：
文献类型：
--
作者：
Tseng, Qingzong;Duchemin-Pelletier, Eve;Thery, Manuel
细胞组织成上皮取决于细胞与细胞外基质（ECM）和相邻细胞的相互作用。细胞-细胞粘附在上皮拓扑结构调节中的作用已被充分描述。ECM更好地促进细胞迁移并为细胞锚定提供结构支架，但其对多细胞形态发生的贡献尚不清楚。我们开发了一个最小的模型系统来研究ECM如何影响细胞间连接的空间组织。纤连蛋白微图案用于限制细胞-ECM粘附的位置。我们发现ECM影响细胞间连接定位的稳定程度以及细胞内和细胞间力的大小。细胞间连接永久性移位，并经历大的垂直张力，只要他们被定位靠近ECM。只有在没有ECM的地区，局势才保持稳定，那里的局势紧张程度较低。ECM的空间组织的异质性诱导细胞中的机械约束的各向异性分布，这似乎适应它们的位置，以最大限度地减少细胞内和细胞间的力。这些结果揭示了ECM在细胞的机械调节和细胞间连接定位中的形态发生作用。
The organization of cells into epithelium depends on cell interaction with both the extracellular matrix (ECM) and adjacent cells. The role of cell-cell adhesion in the regulation of epithelial topology is well-described. ECM is better known to promote cell migration and provide a structural scaffold for cell anchoring, but its contribution to multicellular morphogenesis is less well-understood. We developed a minimal model system to investigate how ECM affects the spatial organization of intercellular junctions. Fibronectin micropatterns were used to constrain the location of cell-ECM adhesion. We found that ECM affects the degree of stability of intercellular junction positioning and the magnitude of intra-and intercellular forces. Intercellular junctions were permanently displaced, and experienced large perpendicular tensional forces as long as they were positioned close to ECM. They remained stable solely in regions deprived of ECM, where they were submitted to lower tensional forces. The heterogeneity of the spatial organization of ECM induced anisotropic distribution of mechanical constraints in cells, which seemed to adapt their position to minimize both intra-and intercellular forces. These results uncover a morphogenetic role for ECM in the mechanical regulation of cells and intercellular junction positioning.