1 Department of Mechanical and Aerospace Engineering, University of California San Diego , San Diego, CA , USA.
2 Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , San Diego, CA , USA.
J R Soc Interface. 2019 Jan 31;16(150):20180675. doi: 10.1098/rsif.2018.0675.
Schistosomiasis is a chronic and morbid disease of poverty affecting approximately 200 million people worldwide. Mature schistosome flatworms wander in the host's hepatic portal and mesenteric venous system where they encounter a range of blood flow conditions and geometrical confinement. However, the mechanisms that support schistosome locomotion and underlie the pathogen's adaptation to its physical environment are largely unknown. By combining microfabrication and traction force microscopy, we developed various in vitro assays to quantify the mechanics of locomotion of adult male Schistosoma mansoni in different physiologically relevant conditions. We show that in unconfined settings, the parasite undergoes two-anchor marching mediated by the coordinated action of its oral and ventral suckers. This mode of locomotion is maintained when the worm faces an external flow, to which it responds by adjusting the strength of its suckers. In geometrically confined conditions, S. mansoni switches to a different crawling modality by generating retrograde peristaltic waves along its body, a mechanism shared with terrestrial and marine worms. However, while the surface of most worms has backward-pointing bristles that rectify peristaltic waves and facilitate forward locomotion, S. mansoni has isotropically oriented tubercles. This requires tight coordination between muscle contraction and substrate friction but gives S. mansoni the ability to reverse its direction of locomotion without turning its body, which is likely advantageous to manoeuvre in narrow-bore vessels. We show that the parasite can also coordinate the action of its suckers with its peristaltic body contractions to increase crawling speed. Throughout this study, we report on a number of biomechanical parameters to quantify the motility of adult schistosomes (e.g. sucker grabbing strength, the rate of detachment under flow, peristaltic wave properties and traction stresses). The new series of in vitro assays make it possible to quantify key phenotypical aspects of S. mansoni motility that could guide the discovery of new drugs to treat schistosomiasis.
血吸虫病是一种慢性和病态的贫困病，影响全球约 2 亿人。成熟的血吸虫扁虫在宿主的肝门静脉和肠系膜静脉系统中游荡，在那里它们遇到一系列血流条件和几何约束。然而，支持血吸虫运动的机制以及病原体适应其物理环境的基础在很大程度上是未知的。通过结合微制造和牵引力显微镜，我们开发了各种体外测定法来量化成年雄性曼氏血吸虫在不同生理相关条件下的运动力学。我们表明，在不受约束的环境中，寄生虫通过其口腔和腹吸盘的协调作用进行双锚定行军。当蠕虫面临外部流动时，它会保持这种运动模式，并通过调整吸盘的强度来响应。在几何约束条件下，曼氏血吸虫通过在其身体上产生逆行蠕动波来切换到不同的爬行模式，这种机制与陆地和海洋蠕虫共享。然而，虽然大多数蠕虫的表面都有向后指向的刚毛，这些刚毛可以纠正蠕动波并促进向前运动，但曼氏血吸虫的刚毛则是各向同性的。这需要肌肉收缩和基质摩擦之间的紧密协调，但赋予了曼氏血吸虫反转运动方向而无需转身的能力，这在狭窄管道中操纵可能是有利的。我们表明，寄生虫还可以协调吸盘的作用及其蠕动的身体收缩，以提高爬行速度。在整个研究过程中，我们报告了许多生物力学参数，以量化成年血吸虫的运动性（例如吸盘抓取强度、在流动下的脱离率、蠕动波特性和牵引力）。新的一系列体外测定法使量化曼氏血吸虫运动的关键表型方面成为可能，这可能有助于发现治疗血吸虫病的新药。
