Adhesion forces and cellular mechano-transduction in parasitic flatworms

Abstract text

Introduction
"Physics of Parasitism" defines the physics and mechanics of parasites interacting with their hosts. Among the most prevalent and medically important groups of trematodes are schistosomes (blood flukes), which live in blood vessels while adult liver flukes live in the bile ducts of their final hosts. The species in focus, Schistosoma mansoni and Fasciola hepatica, exhibit remarkable features such as migratory juvenile stages, and occupation of different host niches (tissues) during their life. In addition, as typical for trematodes, these parasites have head and ventral suckers that aid migration and attachment processes. Although the regulation of biomechanical forces at organ (suckers) and cellular scales (mechanotransduction) is crucial for the survival and infection success of the parasites, these processes are little understood.
Objectives
This project investigates the physical forces occurring at the parasite-host interface by the action of suckers and the mechanisms of force transduction within the parasites. We will study whether adhesion forces differ between different fluke stages, sexes, and species, and whether these forces depend on the physical properties of the parasite"s environment, such as substrate stiffness and flow stress.
Materials & Methods
Traction force microscopy and fluorescence microscopy will be employed to quantify attachment forces of the parasites" suckers to different artificial host-like surfaces in vitro. Fluorescent hydrogels for traction-force measurements will be developed. Likewise, biochips for the culture of parasites under semi-natural conditions will be employed. Cellular proteins involved in mechanotransduction will be functionally analysed by RNA interference and chemical agonists or antagonists.
Results
Initial experiments have been conducted with different formulations of polyethylene glycol- and poly-acrylamide-based hydrogels. Culturing of the parasites in the biochips has been tested. To understand force transduction at a cellular level, mechanosensitive receptors and mechanoresponsive transcriptional regulator proteins have been identified and were successfully knocked down.
Conclusion
Fundamental knowledge on the biomechanics of the adhesion and the cell biology of parasitic flatworms will help to understand the remarkable adaptations of their "bauplan" to their parasitic lifestyle.