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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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Snapshots of several in silico morphotypes during swimming.(a) The bloodstream form. (b) A possible intermediate morphotype in the tsetse fly, where the total cell length is increased by  and the flagellum with the helical half-turn is displaced by  towards the anterior end. (c) A mesocyclic form with a total length of . The flagellum starts at a distance of  from the posterior end and the winding angle of the helical turn is tuned to . (d) A model that resembles an epimastigote form with a total length of , where the attachment of the flagellum is the same as for the mesocyclic form.
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pcbi-1003967-g006: Snapshots of several in silico morphotypes during swimming.(a) The bloodstream form. (b) A possible intermediate morphotype in the tsetse fly, where the total cell length is increased by and the flagellum with the helical half-turn is displaced by towards the anterior end. (c) A mesocyclic form with a total length of . The flagellum starts at a distance of from the posterior end and the winding angle of the helical turn is tuned to . (d) A model that resembles an epimastigote form with a total length of , where the attachment of the flagellum is the same as for the mesocyclic form.

Mentions: To model different morphotypes of the trypanosome, we tuned three morphological parameters: the position where the flagellum starts close to the posterior cell end, the cell length, and the length of the flagellum , which grows with the elongating cell body. To avoid a bending instability of the thin anterior part of the cell body and to make the posterior end stiffer, we increased the bending stiffness by a factor of two. For the wavelength of the bending wave we chose , as before, and also kept the wave frequency constant. Fig. 6 shows snapshots of several in silico morphotypes, which we discuss in the following. Starting at the top, Fig. 6(a) illustrates the model of the bloodstream form used in the previous simulations. We then generate a possible intermediate morphotype in the tsetse fly [see Fig. 6(b)], where we increase the total cell length by to and displace the flagellum with its helical half-turn by towards the anterior end. In Fig. 6(c) we illustrate an adjusted model for a mesocyclic form with a total length of , where the flagellum starts at a distance of from the posterior end and the winding angle of the helical turn is tuned to [see Fig. 6(c)], as explained below. Finally, elongating the cell model further towards the anterior end to a total length of and keeping the same attachment of the flagellum [Fig. 6(d)], results in a model 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)

Snapshots of several in silico morphotypes during swimming.(a) The bloodstream form. (b) A possible intermediate morphotype in the tsetse fly, where the total cell length is increased by  and the flagellum with the helical half-turn is displaced by  towards the anterior end. (c) A mesocyclic form with a total length of . The flagellum starts at a distance of  from the posterior end and the winding angle of the helical turn is tuned to . (d) A model that resembles an epimastigote form with a total length of , where the attachment of the flagellum is the same as for the mesocyclic form.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003967-g006: Snapshots of several in silico morphotypes during swimming.(a) The bloodstream form. (b) A possible intermediate morphotype in the tsetse fly, where the total cell length is increased by and the flagellum with the helical half-turn is displaced by towards the anterior end. (c) A mesocyclic form with a total length of . The flagellum starts at a distance of from the posterior end and the winding angle of the helical turn is tuned to . (d) A model that resembles an epimastigote form with a total length of , where the attachment of the flagellum is the same as for the mesocyclic form.
Mentions: To model different morphotypes of the trypanosome, we tuned three morphological parameters: the position where the flagellum starts close to the posterior cell end, the cell length, and the length of the flagellum , which grows with the elongating cell body. To avoid a bending instability of the thin anterior part of the cell body and to make the posterior end stiffer, we increased the bending stiffness by a factor of two. For the wavelength of the bending wave we chose , as before, and also kept the wave frequency constant. Fig. 6 shows snapshots of several in silico morphotypes, which we discuss in the following. Starting at the top, Fig. 6(a) illustrates the model of the bloodstream form used in the previous simulations. We then generate a possible intermediate morphotype in the tsetse fly [see Fig. 6(b)], where we increase the total cell length by to and displace the flagellum with its helical half-turn by towards the anterior end. In Fig. 6(c) we illustrate an adjusted model for a mesocyclic form with a total length of , where the flagellum starts at a distance of from the posterior end and the winding angle of the helical turn is tuned to [see Fig. 6(c)], as explained below. Finally, elongating the cell model further towards the anterior end to a total length of and keeping the same attachment of the flagellum [Fig. 6(d)], results in a model 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