Modellierung der Fortbewegung des Afrikanischen Trypanosoms

• Antragsteller: Professor Dr. Holger Stark
• Fachliche Zuordnung: Strömungsmechanik ; Statistische Physik, Nichtlineare Dynamik, Komplexe Systeme, Weiche und fluide Materie, Biologische Physik ; Theoretische Chemie: Moleküle, Materialien, Oberflächen
• Förderung: Förderung von 2011 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 193560768

• Erstellungsjahr: 2017

Zusammenfassung der Projektergebnisse

Typanosoma brucei is a uni-cellular parasite that causes the sleeping sickness, a deadly disease for humans that also occurs in livestock. Injected into the mammalian host by the tsetse fly, the trypanosome travels through the blood stream, where it proliferates and ultimately passes the brain-blood barrier. Alternatively, taken up again by a tsetse fly during a bloodmeal, the trypanosome continues its intricate development with several morphological changes to its cell body. During its life cycle the trypanosome meets different microenvironments such as the mammalian’s bloodstream and the tsetse fly’s midgut, proventriculus, foregut, and salivary gland. The elongated cell body of the trypanosome has the shape of a spindle, along which an eukaryotic flagellum is attached with a helical half-turn. A bending wave traveling along the flagellum distorts the whole cell body and thereby propels the trypanosom forward accompanied by rotation about the cell’s long axis. In the project we have developed an accurate, in silico model trypanosome using information from live cell analyses. Performing computer simulations, where the fluid environment is treated by the mesoscale method of multi-particle collision dynamics, we were able to reproduce all motility patterns of the blood-stream form in typical cell culture medium including forward and backward swimming as well as tumbling. Modifying the cell design or generating in silico mutants, we showed that the helical course of the flagellar attachment optimizes the trypanosome’s swimming speed. We also designed trypanosomal morphotypes that occur in the tsetse fly and made predictions for the flagellar attachment in the mesocyclic morphotype. Trypanosomes move in complex environmments such as blood stream or tissue. Our simulations showed that confinement and obstacles are favorable for a trypanosome since they increase the swimming speed. Thus, simulation science provides an investigative tool to systematically explore the morphological diversity during the trypanosome’s life cycle even beyond experimental capabilities. The in silico trypanosome developed in this project might contribute to the unresolved and highly relevant question of how a real trypanosome passes the brain-blood barrier, which ultimately initiates the deadly symptomes of the sleeping sickness. Youtube: https://www.youtube.com/watch?v=my58lrHqGWY

Projektbezogene Publikationen (Auswahl)

• Dynamics of semi-flexible tethered sheets: A simulation study using stochastic rotation dynamics, Eur. Phys. J. E 34, 136 (2011)
  S. B. Babu and H. Stark
  
• Flow loading induces oscillatory trajectories in a bloodstream parasite, Biophys. J. 103, 1162 (2012)
  S. Uppaluri, N. Heddergott, E. Stellamanns, S. Herminghaus, A. Zottl, H. Stark, M. Engstler, and T. Pfohl
  
• Modeling the locomotion of the African trypanosome using multi-particle collision dynamics, New J. Phys. 14, 085012 (2012)
  S. B. Babu and H. Stark
  
• Trypanosome motion represents an adaptation to the crowded environment of the vertebrate bloodstream, PLoS Pathog 8, e1003023 (2012)
  N. Heddergott, T. Krüger, S.B. Babu, A. Weia, E. Stellamans, S. Uppaluri, T. Pfohl, H. Stark, and M. Engstler
  
• Simulating the Complex Cell Design of Trypanosoma brucei and Its Motility, PLoS Comput Biol 11: e1003967 (2015)
  D. Alizadehrad, T. Krüger, M. Engstler, and H. Stark
  
• Taylor line swimming in microchannels and cubic lattices of obstacles, Soft Matter 12, 7350 (2016)
  J. L. Münch, D. Alizadehrad, S. Babu, and H. Stark