The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell–ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the trophoblast model. We found that the spreading area of JAR cells, the formation of focal adhesions, and the polymerization of the F-actin cytoskeleton were all facilitated with increased ECM stiffness. Significantly, JAR cells also exhibited durotactic behavior on ECM with a gradient stiffness. Meanwhile, stiffness of the ECM affects the invasion of multicellular JAR spheroids. These results demonstrated that human trophoblast cells are mechanically sensitive, while the mechanical properties of the uterine microenvironment could play an important role in the implantation process.

中文翻译：

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坚硬的细胞外基质促进滋养层细胞的侵袭行为

细胞外基质 (ECM) 刚度对哺乳动物胚胎植入过程中胚胎滋养层细胞侵袭的影响在很大程度上仍然未知。在这项研究中，我们研究了 ECM 刚度对细胞-ECM 相互作用过程中人类滋养层细胞行为各个方面的影响。通过制造具有不同刚度水平的聚丙烯酰胺 (PA) 水凝胶来模拟子宫的机械微环境。人类绒毛膜癌 (JAR) 细胞谱系用作滋养细胞模型。我们发现 JAR 细胞的扩散区域、粘着斑的形成和 F-肌动蛋白细胞骨架的聚合都随着 ECM 刚度的增加而得到促进。值得注意的是，JAR 细胞还在具有梯度刚度的 ECM 上表现出杜罗行为。同时，ECM 的硬度影响多细胞 JAR 球体的入侵。这些结果表明，人类滋养层细胞具有机械敏感性，而子宫微环境的机械特性可能在着床过程中发挥重要作用。