Structural determinants and function of chirality in the motion of malaria parasites

• Applicants: Professor Dr. Friedrich Frischknecht; Professor Dr. Ulrich Schwarz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Biophysics ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 492010213

Plasmodium sporozoites are the forms of the malaria parasite that are transmitted from the mosquito to the vertebrate host. They are highly polarized cells and migrate on substrates in a chiral way, similar to most extracellular forms of apicomplexans. The overall aims of this project are to quantify the chiral motion of sporozoites in 2D and 3D, to identify its structural basis and to establish its biological relevance for successful invasions. We tackle this challenge by combining quantitative experimentation with image processing and mathematical models. In the first funding period, we found that sporozoites all move in right-handed helical trajectories in isotropic hydrogels and circle in clockwise direction when they hit the glass substrate, exactly opposite as they would when circling on a glass substrate in medium. This suggests that on glass sporozoites move on their back and not on their belly, as formerly assumed. To describe this motion, we developed two mathematical models for chirality in gliding. One of these predicted the overall movements that we found experimentally. This chiral adhesion model suggests that more adhesins are placed at the surface facing the substrate for 2D motility and at the surface facing the back of the helical trajectories during 3D motility. In the second funding period, we will test these and other predictions, using such experimental methods as traction force microscopy, super-resolution, electron and expansion microscopies, as well as two-photon laser printing of obstacles. To obtain a deeper understanding, we will further develop our mathematical models based on the experimental results, including active particle models for collisions and micromechanical models for cell mechanics. In general, we aim to prove that sporozoites have evolved curved shapes and chiral motion patterns based on surface flow of adhesins to achieve stable movement in challenging extracellular environments.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2332: Physics of Parasitism