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Simulating the complex cell design of Trypanosoma brucei and its motility.

Alizadehrad D, Krüger T, Engstler M, Stark H - PLoS Comput. Biol. (2015)

Bottom Line: As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Theoretical Physics, Technische Universität Berlin, Berlin, Germany.

ABSTRACT
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.

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Swimming velocity versus flagellar winding angle for the mesocyclic form.Rescaled swimming velocity  plotted versus winding angle . The snapshots show the model trypanosome for winding angles , , and . Inset: Rescaled end-to-end distance of the cell body, , versus .
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pcbi-1003967-g007: Swimming velocity versus flagellar winding angle for the mesocyclic form.Rescaled swimming velocity plotted versus winding angle . The snapshots show the model trypanosome for winding angles , , and . Inset: Rescaled end-to-end distance of the cell body, , versus .

Mentions: To model the mesocyclic morphotype, we started with a helical half-turn of the flagellum and observed that the cell moved slower than the real mesocyclic form in experiments. We attributed this to the stronger bending of the simulated cell body compared to the real cell. Already in Figs. 5(c) and (d) we have demonstrated that stronger bending decreases the swimming velocity. We therefore decided to decrease the winding angle of the helical flagellar turn, which indeed lowered the bend of the cell body or increased the mean end-to-end distance , as the inset of Fig. 7 demonstrates. In parallel with the smaller bend, the cell becomes more straight and hence its hydrodynamic friction decreases. This, in turn, increases the swimming velocity (see Fig. 7). At angles around the flagellar bending wave produces the most realistic swimming pattern compared to the swimming mesocyclic trypanosome in experiments (see S8 Video), where speed and end-to-end distance of the model and the real trypanosome agree with each other. Also the rotational velocity of the cell body, which is lower than in the blood stream form due to the smaller helical turn, agrees well with experiments. In order to reduce the bend of the model trypanosome, other modifications of the cell body such as varying the stiffness of the cell or the amplitude of the flagellar wave were not successful. So we think that the reduced helical turn makes a solid prediction for the morphology of the mesocyclic cell. Last but not least, S9 Video presents our swimming in silico version that resembles an epimastigote form.


Simulating the complex cell design of Trypanosoma brucei and its motility.

Alizadehrad D, Krüger T, Engstler M, Stark H - PLoS Comput. Biol. (2015)

Swimming velocity versus flagellar winding angle for the mesocyclic form.Rescaled swimming velocity  plotted versus winding angle . The snapshots show the model trypanosome for winding angles , , and . Inset: Rescaled end-to-end distance of the cell body, , versus .
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288712&req=5

pcbi-1003967-g007: Swimming velocity versus flagellar winding angle for the mesocyclic form.Rescaled swimming velocity plotted versus winding angle . The snapshots show the model trypanosome for winding angles , , and . Inset: Rescaled end-to-end distance of the cell body, , versus .
Mentions: To model the mesocyclic morphotype, we started with a helical half-turn of the flagellum and observed that the cell moved slower than the real mesocyclic form in experiments. We attributed this to the stronger bending of the simulated cell body compared to the real cell. Already in Figs. 5(c) and (d) we have demonstrated that stronger bending decreases the swimming velocity. We therefore decided to decrease the winding angle of the helical flagellar turn, which indeed lowered the bend of the cell body or increased the mean end-to-end distance , as the inset of Fig. 7 demonstrates. In parallel with the smaller bend, the cell becomes more straight and hence its hydrodynamic friction decreases. This, in turn, increases the swimming velocity (see Fig. 7). At angles around the flagellar bending wave produces the most realistic swimming pattern compared to the swimming mesocyclic trypanosome in experiments (see S8 Video), where speed and end-to-end distance of the model and the real trypanosome agree with each other. Also the rotational velocity of the cell body, which is lower than in the blood stream form due to the smaller helical turn, agrees well with experiments. In order to reduce the bend of the model trypanosome, other modifications of the cell body such as varying the stiffness of the cell or the amplitude of the flagellar wave were not successful. So we think that the reduced helical turn makes a solid prediction for the morphology of the mesocyclic cell. Last but not least, S9 Video presents our swimming in silico version that resembles an epimastigote form.

Bottom Line: As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Theoretical Physics, Technische Universität Berlin, Berlin, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus