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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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Comparison of the model and a real trypanosome during swimming motion (A–D).The swimming trajectory and dynamic shape of the simulated model trypanosome (top row) compares well with the forward swimming motion of the real trypanosome (middle and bottom row). Snapshots of the real trypanosome are taken at the indicated times from S4 Video. Fluorescently labelled surface (middle row) or untreated cells (bottom row) were recorded by high speed microscopy (200–500 frames per second). The cells, which exhibit similar speeds and rotational frequencies, show matching cell body conformations at all times over a swimming path of several cell lengths. These periodically repeating shape conformations are initiated by the bending wave passing along the flagellum and determine the trajectory of the swimming parasite.
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pcbi-1003967-g002: Comparison of the model and a real trypanosome during swimming motion (A–D).The swimming trajectory and dynamic shape of the simulated model trypanosome (top row) compares well with the forward swimming motion of the real trypanosome (middle and bottom row). Snapshots of the real trypanosome are taken at the indicated times from S4 Video. Fluorescently labelled surface (middle row) or untreated cells (bottom row) were recorded by high speed microscopy (200–500 frames per second). The cells, which exhibit similar speeds and rotational frequencies, show matching cell body conformations at all times over a swimming path of several cell lengths. These periodically repeating shape conformations are initiated by the bending wave passing along the flagellum and determine the trajectory of the swimming parasite.

Mentions: We generate a sinusoidal bending wave along the flagellum, which runs from the thinner anterior tip of the cell body to the posterior end (tip-to-base beat). The bending amplitude decreases towards the posterior end to better match the shape changes of the real trypanosome. The wavelength , where is the length of the cell body, is adjusted to the real system and the experimental wave frequency sets the relevant time scale [4]. The cell body distorts in response to the flagellar wave, which generates translational motion in the anterior direction opposite to the wave direction (see S2 Video). Due to the helical flagellar attachment, the cell body assumes an overall asymmetric chiral shape [see Fig. 1(b),(c)] typical of a real trypanosome [see Fig. 1(d),(e)]. To quantify the chiral shape, we determined the centerline of the model cell body, reaching from the posterior to the anterior end, and calculated the torsion averaged over the full length and over several time periods. As shown in the Section Flagellar attachment optimizes swimming, the non-zero mean torsion at the flagellar winding angle clearly indicates the overall chiral shape. Therefore, it rotates counterclockwise about the long axis of the cell, when viewed in the direction of motion (S2 Video). Typically, for a full turn periods of the bending wave are needed in medium with the viscosity of blood [4]. Note, when the flagellar attachment is completely straight [winding angle ], the mean torsion and hence the rotational speed are zero. In order to obtain a realistic motility pattern, the simulation model was empirically optimized to meet real life conditions. We adjusted the flexibility of the cell body accordingly by changing the elastic properties of the surface mesh and tuned the bending amplitude of the sinusoidal flagellar wave. Ultimately, this led to a realistic realization of the motility pattern of an African trypanosome as Fig. 2 and Videos S3 and S4 demonstrate.


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

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

Comparison of the model and a real trypanosome during swimming motion (A–D).The swimming trajectory and dynamic shape of the simulated model trypanosome (top row) compares well with the forward swimming motion of the real trypanosome (middle and bottom row). Snapshots of the real trypanosome are taken at the indicated times from S4 Video. Fluorescently labelled surface (middle row) or untreated cells (bottom row) were recorded by high speed microscopy (200–500 frames per second). The cells, which exhibit similar speeds and rotational frequencies, show matching cell body conformations at all times over a swimming path of several cell lengths. These periodically repeating shape conformations are initiated by the bending wave passing along the flagellum and determine the trajectory of the swimming parasite.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003967-g002: Comparison of the model and a real trypanosome during swimming motion (A–D).The swimming trajectory and dynamic shape of the simulated model trypanosome (top row) compares well with the forward swimming motion of the real trypanosome (middle and bottom row). Snapshots of the real trypanosome are taken at the indicated times from S4 Video. Fluorescently labelled surface (middle row) or untreated cells (bottom row) were recorded by high speed microscopy (200–500 frames per second). The cells, which exhibit similar speeds and rotational frequencies, show matching cell body conformations at all times over a swimming path of several cell lengths. These periodically repeating shape conformations are initiated by the bending wave passing along the flagellum and determine the trajectory of the swimming parasite.
Mentions: We generate a sinusoidal bending wave along the flagellum, which runs from the thinner anterior tip of the cell body to the posterior end (tip-to-base beat). The bending amplitude decreases towards the posterior end to better match the shape changes of the real trypanosome. The wavelength , where is the length of the cell body, is adjusted to the real system and the experimental wave frequency sets the relevant time scale [4]. The cell body distorts in response to the flagellar wave, which generates translational motion in the anterior direction opposite to the wave direction (see S2 Video). Due to the helical flagellar attachment, the cell body assumes an overall asymmetric chiral shape [see Fig. 1(b),(c)] typical of a real trypanosome [see Fig. 1(d),(e)]. To quantify the chiral shape, we determined the centerline of the model cell body, reaching from the posterior to the anterior end, and calculated the torsion averaged over the full length and over several time periods. As shown in the Section Flagellar attachment optimizes swimming, the non-zero mean torsion at the flagellar winding angle clearly indicates the overall chiral shape. Therefore, it rotates counterclockwise about the long axis of the cell, when viewed in the direction of motion (S2 Video). Typically, for a full turn periods of the bending wave are needed in medium with the viscosity of blood [4]. Note, when the flagellar attachment is completely straight [winding angle ], the mean torsion and hence the rotational speed are zero. In order to obtain a realistic motility pattern, the simulation model was empirically optimized to meet real life conditions. We adjusted the flexibility of the cell body accordingly by changing the elastic properties of the surface mesh and tuned the bending amplitude of the sinusoidal flagellar wave. Ultimately, this led to a realistic realization of the motility pattern of an African trypanosome as Fig. 2 and Videos S3 and S4 demonstrate.

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