The eggs of the parasitic blood fluke, Schistosoma, are the main drivers of the chronic pathologies associated with schistosomiasis, a disease of poverty afflicting approximately 220 million people worldwide. Eggs laid by Schistosoma mansoni in the bloodstream of the host are encapsulated by vascular endothelial cells (VECs), the first step in the migration of the egg from the blood stream into the lumen of the gut and eventual exit from the body. The biomechanics associated with encapsulation and extravasation of the egg are poorly understood. We demonstrate that S. mansoni eggs induce VECs to form two types of membrane extensions during encapsulation; filopodia that probe eggshell surfaces and intercellular nanotubes that presumably facilitate VEC communication. Encapsulation efficiency, the number of filopodia and intercellular nanotubes, and the length of these structures depend on the egg’s vitality and, to a lesser degree, its maturation state. During encapsulation, live eggs induce VEC contractility and membranous structures formation, in a Rho/ROCK pathway-dependent manner. Using elastic hydrogels embedded with fluorescent microbeads as substrates to culture VECs, live eggs induce VECs to exert significantly greater contractile forces during encapsulation than dead eggs, which leads to 3D deformations on both the VEC monolayer and the flexible substrate underneath. These significant mechanical deformations cause the VEC monolayer tension to fluctuate with eventual rupture of VEC junctions, thus facilitating egg transit out of the blood vessel. Overall, our data on the mechanical interplay between host VECs and the schistosome egg improve our understanding of how this parasite manipulates its immediate environment to maintain disease transmission.

中文翻译：

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曼氏血吸虫卵与血管内皮细胞的生物力学相互作用促进卵外渗

血吸虫寄生血吸虫的卵是与血吸虫病相关的慢性病状的主要驱动因素，血吸虫病是一种影响全球约 2.2 亿人的贫困疾病。曼氏血吸虫在宿主血流中产下的卵被血管内皮细胞 (VEC) 包裹，这是卵从血流迁移到肠腔并最终离开身体的第一步。与卵的包裹和外渗相关的生物力学知之甚少。我们证明了S. mansoni卵在封装过程中诱导 VEC 形成两种类型的膜延伸；探测蛋壳表面的丝状伪足和可能促进 VEC 通信的细胞间纳米管。封装效率、丝状伪足和细胞间纳米管的数量以及这些结构的长度取决于卵的活力，并在较小程度上取决于其成熟状态。在封装期间，活卵以 Rho/ROCK 通路依赖性方式诱导 VEC 收缩性和膜结构形成。使用嵌入有荧光微珠的弹性水凝胶作为培养 VEC 的底物，活卵诱导 VEC 在封装过程中比死卵发挥更大的收缩力，这会导致 VEC 单层和下面的柔性基底上的 3D 变形。这些显着的机械变形导致 VEC 单层张力随着 VEC 连接处的最终破裂而波动，从而促进卵子从血管中运输出来。总的来说，我们关于宿主 VEC 和血吸虫卵之间机械相互作用的数据提高了我们对这种寄生虫如何操纵其直接环境以维持疾病传播的理解。