Parasitic flatworms (platyhelminths) affect the health of humans and animals alike. In their host, these parasites migrate to their preferred organ in order to feed on host cells and sexually reproduce. This project focuses on two important flatworm members, the blood fluke Schistosoma mansoni and the commong liver fluke Fasciola hepatica, which finally reside in mesenteric veins and bile ducts, respectively. Common features of these parasites are suckers, which aid in locomotion and food ingestion, but thereby may mechanically damage host tissues. Although suckers are essential morphological structures of parasitic flukes, their biomechanical properties and the forces acting on host cells are little understood. The same accounts for the biophysical properties of the structured bioactive surface of flatworms, the so-called tegument, which is in contact with host tissue. In addition, the parasites themselves are likely to experience biomechanical forces, on the one hand internally during organ growth, on the other hand at their surface by the surrounding blood or bile flow. Schistosomes are remarkable in another aspect, as the physical contact of the female parasite with a male partner is a prerequisite for the females’ sexual maturation. In this project, we address the hypothesis that physical forces fundamentally influence flatworm biology as well as the physiology of cells to which these parasites attach. With respect to biophysics, we will answer the following questions: (i) Which forces act on the female schistosome by the body of the male partner? (ii) Do biophysical properties of certain parasite tissues change during growth or maturation? (iii) Do parasitic flatworms cause traction stress in host cell layers? In addition, we will address the following questions regarding the cellular mechanobiology: (iv) How do parasite cells and host cells respond to physical forces on a physiological and molecular level? (v) Do these responses depend on the cell type? In an interdisciplinary approach, we will combine methods of parasitology with soft matter engineering and biophysical methods (traction force and atomic force microscopy, optical diffraction and micro-computed tomography). We will mimic the parasite environment and host-parasite interface by making use of modified hydrogels and a microfluidics-based biochip system (“worm-on-a-chip”), and develop a method toolbox to study the mechanobiology in parasitic flatworms. Knowledge on the biomechanical forces acting on platyhelminths and host cells and the molecular consequences will improve our basic understanding of parasite development and parasite-host interaction.
DFG Programme
Priority Programmes
