Simulating the complex cell design of Trypanosoma brucei and its motility
| Autor: | Timothy Krüger, Markus Engstler, Holger Stark, Davod Alizadehrad |
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| Rok vydání: | 2015 |
| Předmět: |
Life Cycles
Medical Physics sleeping sickness Biophysics Theory Cell Movement Flagellar Rotation Biological Fluid Mechanics Morphogenesis Medicine and Health Sciences Cell Mechanics Biomechanics Flagellate lcsh:QH301-705.5 Mathematical Physics Ecology biology elastic network model Physics Microbial Growth and Development Complex cell Cell Motility medicine.anatomical_structure Computational Theory and Mathematics Modeling and Simulation Physical Sciences Engineering and Technology Fluidics Biological system Research Article Biotechnology Computer Modeling 570 Biowissenschaften Biologie Biophysical Simulations Computer and Information Sciences In silico Parasitic Life Cycles Trypanosoma brucei brucei Biophysics Motility Bioengineering Cell Migration Flagellum Trypanosoma brucei Microbiology Models Biological flagellate Cellular and Molecular Neuroscience ddc:570 Evolutionary Modeling Genetics medicine Parasitic Diseases Computer Simulation simulation science Parasite Evolution Molecular Biology Theoretical Biology Ecology Evolution Behavior and Systematics Swimming Evolutionary Biology Mechanism (biology) Biological Locomotion Evolutionary Developmental Biology Biology and Life Sciences Computational Biology Cell Biology biology.organism_classification Computing Methods lcsh:Biology (General) Trypanosoma Parasitology Developmental Biology |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 11, Iss 1, p e1003967 (2015) |
| DOI: | 10.14279/depositonce-7036 |
| Popis: | The flagellate Trypanosoma brucei, which causes the sleeping sickness when infecting a mammalian host, goes through an intricate life cycle. It has a rather complex propulsion mechanism and swims in diverse microenvironments. These continuously exert selective pressure, to which the trypanosome adjusts with its architecture and behavior. As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle. However, although cell biology has detailed form and function of most of them, experimental data on the dynamic behavior and development of most morphotypes is lacking. Here we show that simulation science can predict intermediate cell designs by conducting specific and controlled modifications of an accurate, nature-inspired cell model, which we developed using information from live cell analyses. The cell models account for several important characteristics of the real trypanosomal morphotypes, such as the geometry and elastic properties of the cell body, and their swimming mechanism using an eukaryotic flagellum. We introduce an elastic network model for the cell body, including bending rigidity and simulate swimming in a fluid environment, using the mesoscale simulation technique called multi-particle collision dynamics. The in silico trypanosome of the bloodstream form displays the characteristic in vivo rotational and translational motility pattern that is crucial for survival and virulence in the vertebrate host. Moreover, our model accurately simulates the trypanosome's tumbling and backward motion. We show that the distinctive course of the attached flagellum around the cell body is one important aspect to produce the observed swimming behavior in a viscous fluid, and also required to reach the maximal swimming velocity. Changing details of the flagellar attachment generates less efficient swimmers. We also simulate different morphotypes that occur during the parasite's development in the tsetse fly, and predict a flagellar course we have not been able to measure in experiments so far. Author Summary 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 can be taken up again by a fly during a bloodmeal. In the tsetse fly, it continues its development with several morphological changes to the cell body plan. 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 cell body of the trypanosome has the shape of a spindle along which an eukaryotic flagellum is attached. We have developed an accurate, in silico model trypanosome using information from live cell analyses. Performing computer simulations, we are able to reproduce all motility patterns of the blood-stream form in typical cell culture medium. Modifying the cell design, we show that the helical course of the flagellar attachment optimizes the trypanosome's swimming speed. We also design trypanosomal morphotypes that occur in the tsetse fly. Simulation science thereby provides an investigative tool to systematically explore the morphologcial diversity during the trypanosome's life cycle even beyond experimental capabilities. |
| Databáze: | OpenAIRE |
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