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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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Related in: MedlinePlus

Swimming velocity versus the ratio of angular frequencies for counterpropagating flagellar waves.Rescaled swimming velocity  plotted versus the ratio  of angular frequencies for simultaneous base-to-tip () and tip-to-base () propagating flagellar waves. Inset: Orientational correlations of the end-to-end vector, , for two ratios of frequency.
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pcbi-1003967-g004: Swimming velocity versus the ratio of angular frequencies for counterpropagating flagellar waves.Rescaled swimming velocity plotted versus the ratio of angular frequencies for simultaneous base-to-tip () and tip-to-base () propagating flagellar waves. Inset: Orientational correlations of the end-to-end vector, , for two ratios of frequency.

Mentions: We implemented bending waves travelling along the flagellum in both directions with increasing amplitude towards the tip. For both waves we chose the same wavelength . We kept the frequency of the tip-to-base wave fixed and varied the frequency or velocity of the base-to-tip wave. Fig. 4 plots the reduced swimming velocity versus the ratio of both frequencies, . For , where we did not implement any base-to-tip wave, the trypanosome performs its standard motion in forward direction. At a ratio of , the swimming velocity is reduced to half the value and in the interval between and 1.66 persistent swimming stops completely. For larger wave frequencies the swimming direction is even reversed as dictated by the base-to-tip wave. S5 Video shows both a real tumbling trypanosome in cell culture medium and the tumbling model trypanosome at . Both videos demonstrate with striking similarity the irregular motion and directional changes of a trypanosome. To quantify the directional persistence in the swimming motion, we determined the vector connecting both ends of the trypanosome. In the inset of Fig. 4 we plot the time-autocorrelation function for the orientation of the trypanosome, , where and means average over reference time and several simulation runs [39]. Tumbling at is indicated by a complete loss of orientational correlations after ca. three wave periods, whereas directional swimming at only shows a small decay, mostly due to the fact that the trypanosome does not swim on a perfectly regular helical trajectory, whereas small scale oscillations originate from periodic cell deformations. To conclude, our results demonstrate that disturbing the forward flagellar wave by a base-to-tip wave strongly affects the trypanosome motility pattern.


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 the ratio of angular frequencies for counterpropagating flagellar waves.Rescaled swimming velocity  plotted versus the ratio  of angular frequencies for simultaneous base-to-tip () and tip-to-base () propagating flagellar waves. Inset: Orientational correlations of the end-to-end vector, , for two ratios of frequency.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003967-g004: Swimming velocity versus the ratio of angular frequencies for counterpropagating flagellar waves.Rescaled swimming velocity plotted versus the ratio of angular frequencies for simultaneous base-to-tip () and tip-to-base () propagating flagellar waves. Inset: Orientational correlations of the end-to-end vector, , for two ratios of frequency.
Mentions: We implemented bending waves travelling along the flagellum in both directions with increasing amplitude towards the tip. For both waves we chose the same wavelength . We kept the frequency of the tip-to-base wave fixed and varied the frequency or velocity of the base-to-tip wave. Fig. 4 plots the reduced swimming velocity versus the ratio of both frequencies, . For , where we did not implement any base-to-tip wave, the trypanosome performs its standard motion in forward direction. At a ratio of , the swimming velocity is reduced to half the value and in the interval between and 1.66 persistent swimming stops completely. For larger wave frequencies the swimming direction is even reversed as dictated by the base-to-tip wave. S5 Video shows both a real tumbling trypanosome in cell culture medium and the tumbling model trypanosome at . Both videos demonstrate with striking similarity the irregular motion and directional changes of a trypanosome. To quantify the directional persistence in the swimming motion, we determined the vector connecting both ends of the trypanosome. In the inset of Fig. 4 we plot the time-autocorrelation function for the orientation of the trypanosome, , where and means average over reference time and several simulation runs [39]. Tumbling at is indicated by a complete loss of orientational correlations after ca. three wave periods, whereas directional swimming at only shows a small decay, mostly due to the fact that the trypanosome does not swim on a perfectly regular helical trajectory, whereas small scale oscillations originate from periodic cell deformations. To conclude, our results demonstrate that disturbing the forward flagellar wave by a base-to-tip wave strongly affects the trypanosome motility pattern.

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