Biomechanics of the Platyhelminth Adhesion, Locomotion, and Reproduction

血吸虫和肝吸虫是寄生性扁形虫，它们感染哺乳动物宿主，在其中生长、进食、繁殖并最终引起慢性传染病。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，这是本项目的重点。这些扁形虫有两个吸盘，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，但其基于吸盘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功能：雌雄寄生虫之间的密切和持续的身体接触对雌性性成熟至关重要。该项目研究了寄生虫粘附，运动和繁殖的基本生物力学原理：通过吸盘的作用在寄生虫-宿主界面发生的物理力，以及作用在寄生虫-寄生虫界面的不断配对的寄生虫夫妇的物理力。要回答的生物物理问题是：（一）不同的吸虫阶段，性别和物种之间的粘附力和运动模式不同？(ii)这些力是否取决于寄生虫环境的物理特性，例如基底刚度和流动应力？(iii)作用在寄生虫夫妇身上的力量会影响雌性寄生虫的生殖能力吗？(iv)哪些力量通过男性伴侣的身体作用于女性的身体？为了可视化，量化和数学建模这些力量，我们将团结在一个跨学科的方法软物质工程的机械响应聚合物水凝胶与基于微流体的生物芯片系统（“蠕虫芯片”），牵引力显微镜，蠕虫学，体外技术，和先进的三维断层成像。了解寄生虫粘附、运动和繁殖的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宿主生境适应的理解。

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.