Biomechanics of the Platyhelminth Adhesion, Locomotion, and Reproduction

血吸虫和肝吸虫是寄生的扁虫，它们会感染哺乳动物宿主，在宿主中生长、喂养、繁殖，并最终导致慢性传染病。影响人类的两种高度流行和医学上重要的物种是曼氏血吸虫和肝片吸虫，它们是本项目的重点。这些扁虫有两个吸盘，使寄生虫能够移动到宿主体内的最终目的地，并以宿主组织为食。虽然吸盘是这类寄生虫的基本形态结构，但其以吸盘为基础的粘附系统的生物力学知之甚少。血吸虫还表现出另一个重要的生物学特征：雄性和雌性寄生虫之间的近距离和持续的身体接触对雌性性成熟至关重要。本项目研究了促进寄生虫粘附、运动和繁殖的基本生物力学原理：吸盘作用于寄生虫-宿主界面的物理力，以及持续配对的血吸虫夫妇作用于寄生虫-寄生虫界面的物理力。需要回答的生物物理问题是：(i)不同阶段、性别和物种的吸虫粘附力和运动模式是否不同？（ii）这些力是否取决于寄生虫所处环境的物理特性，如基质刚度和流动应力？（三）作用于血吸虫夫妇的力量是否影响雌性寄生虫的生殖能力？（四）男性伴侣的身体对雌性血吸虫起哪些作用？为了可视化、量化和数学建模这些力，我们将结合跨学科方法，将机械响应聚合物水凝胶软物质工程与基于微流体的生物芯片系统（“芯片上的蠕虫”）、牵引力显微镜、蠕虫学、体外技术和先进的基于3D断层成像技术结合起来。了解寄生虫粘附、运动和繁殖的潜在生物物理机制将有助于扩大对寄生虫成功进化及其对不同寄主栖息地的适应的理解。

Blood flukes and liver flukes are parasitic flatworms that infect mammalian hosts in which they grow, feed, reproduce, and ultimately cause chronic infectious diseases. Two of the highly prevalent and medically important species affecting humans are Schistosoma mansoni and Fasciola hepatica that are in the focus of this project. These flatworms own two suckers that enable the parasite to move to its final destinations within the host and to feed on host tissues. Although suckers are essential morphological structures of this class of parasites, the biomechanics of their suction-based adhesion system is little understood. Schistosomes exhibit another important biological feature: proximate and constant physical contact between male and female parasite are essential for female sexual maturation. This project investigates fundamental biomechanical principles contributing to parasite adhesion, locomotion, and reproduction: physical forces occurring at the parasite-host interface by the action of suckers, and physical forces acting at the parasite-parasite interface of the constantly paired schistosome couple. The biophysical questions to be answered are: (i) Do adhesion forces and locomotion patterns differ between different fluke stages, sexes and species? (ii) Do these forces depend on the physical properties of the parasite’s environment, such as substrate stiffness and flow stress? (iii) Do forces that act on the schistosome couple influence the reproductive capacity of the female parasite? (iv) And which forces act on the female schistosome by the body of the male partner? To visualize, quantify and mathematically model these forces, we will unite in an interdisciplinary approach soft matter engineering of mechano-responsive polymeric hydrogels with microfluidics-based biochip systems (“worm-on-a-chip”), traction force microscopy, helminthology, in-vitro techniques, and advanced 3D tomography-based imaging. Knowing the underlying biophysical mechanisms of adhesion, locomotion and reproduction will help to expand the understanding of the parasites’ successful evolution and their adaptations to different host habitats.