An in silico model of the African trypanosome: Moving in complex environments

• Applicant: Professor Dr. Holger Stark
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504947458

The African trypanosome, a uni-cellular parasite and an exceptional microswimmer, causes the live threatening sleeping sickness in humans. It uses an eukaryotic flagellum firmly attached to its spindle-shaped cell body so that a bending wave propagating along the flagellum distorts the whole cell body and thereby propels the trypanosome forward. Trypanosomes not only move through blood vesses, but they also have to navigate in tissues such as the skin, fat tissue, and organs, where they also encounter interstitial flow. They move around cells through the extracellular matrix, an elastic fiber network such as collagen, or they have to squeeze through narrow passages between cells, also on their way to the brain, and they swim through lymph vessels that contain valves.In the terminated funding period of this project, we started to investigate how the trypanosome moves in such confining and complex environments based on an in silico model, which we developed earlier in collaboration with the group of M. Engstler (Würzburg). In the new funding period of this renewal proposal, we plan to continue this study also collaborating with the group of M. Weiss (Bayreuth).The complex environments that the trypanosome encounters are governed by two principles: geometry and deformability, which we will investigate in generic situations with increasing complexity, also in the presence of flow. For this purpose, we rely on our in silico model trypanosome in hydrodynamic simulations using the method of multi-particle collision dynamics. We will investigate how the model trypanosome squeezes through the narrow passage of two deformable obstacles and how it opens a bendable valve in a channel mimicking a lymph vessel. We then continue to thoroughly investigate the swimming path of the trypanosome in elastic fiber networks as a model for collagen, which we construct from bead-spring chains with bending rigidity. Finally, we address aspects of navigating in tissue, concentrating on the packing and deformability of cells. We mimic these properties by ordered and disordered lattices of deformable obstacles of cylindrical shape. Our investigations will bring us closer to an understanding how trypanosomes move in different types of tissue.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Markus Engstler; Professor Dr. Matthias Weiss