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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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The model trypanosome and a real trypanosome.(a) Cell body of the model trypanosome without distortion. The elastic network made from vertices connected by springs defines the surface. The blue line connecting a series of vertices represents the flagellum with the helical half-turn. (b, c) Snapshots of the model trypanosome during simulated swimming motion. (d) 3d volume model of a live trypanosome with fluorescently labeled surface. (e) 3d surface model of the cell in (d), with the flagellum highlighted in blue. (f) The same surface model rotated about the horizontal, in order to get a better view on the left-handed half-turn of the flagellum indicated in red.
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pcbi-1003967-g001: The model trypanosome and a real trypanosome.(a) Cell body of the model trypanosome without distortion. The elastic network made from vertices connected by springs defines the surface. The blue line connecting a series of vertices represents the flagellum with the helical half-turn. (b, c) Snapshots of the model trypanosome during simulated swimming motion. (d) 3d volume model of a live trypanosome with fluorescently labeled surface. (e) 3d surface model of the cell in (d), with the flagellum highlighted in blue. (f) The same surface model rotated about the horizontal, in order to get a better view on the left-handed half-turn of the flagellum indicated in red.

Mentions: To simulate and analyze the trypanosome's swimming mechanism, we constructed a refined elastic network model of the trypanosome based on experimental data from advanced video microscopy. A full description of the model is presented in the Section Materials and Methods. We simulated the fluid environment with a mesoscale simulation technique for solving the Navier-Stokes equation called multi-particle collision dynamics (MPCD) [29]–[32]. The trypanosome has a spindle-shaped elongated cell body with tapered ends. The cell body is about long, has a diameter of ca. at the thickest part in the posterior section, and becomes thinner towards both ends, in particular, towards the long anterior end [4], [5]. Correspondingly, our model trypanosome has circular cross sections of varying diameter and the cell surface is defined by a mesh of points which are connected by harmonic springs spanning also in the cross-sectional planes [see Fig. 1(a)]. Together with additional bending rigidity, we obtain a cell body with precisely controllable flexibility. The actuating flagellum is attached to the cell body, which distorts in response to the bending wave running along the flagellum [see Fig. 1(b),(c)]. To adjust the course of the flagellum on the cell surface, we applied results from a detailed morphometric analysis using fluorescence microscopy [4]. An example for a cell body with fluorescently labeled surface is shown in Fig. 1(d) and in S1 Video. The rendered cell surface in Fig. 1(e) highlights the course of the attached flagellum and in Fig. 1(f) the whole cell is rotated by about the horizontal. From a careful inspection of such images the following flagellar course for the cell model evolved [see Fig. 1(a)]: The flagellum originates from the flagellar pocket at the posterior end of the cell, follows a small straight segment and then wraps around the cell body with a left-handed half-turn. Altogether this needs a length of ca. [4]. The flagellum then follows a straight path along the thinning anterior part of the cell body and protrudes freely at the anterior end. In the experimental images of Fig. 1(f) and S1 Video, the helical segment of the attached flagellum is marked red.


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

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

The model trypanosome and a real trypanosome.(a) Cell body of the model trypanosome without distortion. The elastic network made from vertices connected by springs defines the surface. The blue line connecting a series of vertices represents the flagellum with the helical half-turn. (b, c) Snapshots of the model trypanosome during simulated swimming motion. (d) 3d volume model of a live trypanosome with fluorescently labeled surface. (e) 3d surface model of the cell in (d), with the flagellum highlighted in blue. (f) The same surface model rotated about the horizontal, in order to get a better view on the left-handed half-turn of the flagellum indicated in red.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4288712&req=5

pcbi-1003967-g001: The model trypanosome and a real trypanosome.(a) Cell body of the model trypanosome without distortion. The elastic network made from vertices connected by springs defines the surface. The blue line connecting a series of vertices represents the flagellum with the helical half-turn. (b, c) Snapshots of the model trypanosome during simulated swimming motion. (d) 3d volume model of a live trypanosome with fluorescently labeled surface. (e) 3d surface model of the cell in (d), with the flagellum highlighted in blue. (f) The same surface model rotated about the horizontal, in order to get a better view on the left-handed half-turn of the flagellum indicated in red.
Mentions: To simulate and analyze the trypanosome's swimming mechanism, we constructed a refined elastic network model of the trypanosome based on experimental data from advanced video microscopy. A full description of the model is presented in the Section Materials and Methods. We simulated the fluid environment with a mesoscale simulation technique for solving the Navier-Stokes equation called multi-particle collision dynamics (MPCD) [29]–[32]. The trypanosome has a spindle-shaped elongated cell body with tapered ends. The cell body is about long, has a diameter of ca. at the thickest part in the posterior section, and becomes thinner towards both ends, in particular, towards the long anterior end [4], [5]. Correspondingly, our model trypanosome has circular cross sections of varying diameter and the cell surface is defined by a mesh of points which are connected by harmonic springs spanning also in the cross-sectional planes [see Fig. 1(a)]. Together with additional bending rigidity, we obtain a cell body with precisely controllable flexibility. The actuating flagellum is attached to the cell body, which distorts in response to the bending wave running along the flagellum [see Fig. 1(b),(c)]. To adjust the course of the flagellum on the cell surface, we applied results from a detailed morphometric analysis using fluorescence microscopy [4]. An example for a cell body with fluorescently labeled surface is shown in Fig. 1(d) and in S1 Video. The rendered cell surface in Fig. 1(e) highlights the course of the attached flagellum and in Fig. 1(f) the whole cell is rotated by about the horizontal. From a careful inspection of such images the following flagellar course for the cell model evolved [see Fig. 1(a)]: The flagellum originates from the flagellar pocket at the posterior end of the cell, follows a small straight segment and then wraps around the cell body with a left-handed half-turn. Altogether this needs a length of ca. [4]. The flagellum then follows a straight path along the thinning anterior part of the cell body and protrudes freely at the anterior end. In the experimental images of Fig. 1(f) and S1 Video, the helical segment of the attached flagellum is marked red.

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