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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 sperm number.Rescaled swimming velocity  plotted versus sperm number  (double-logarithmic plot) for to two viscosity values  (squares) and  (triangles) given in MPCD units. Inset: Number of flagellar beats per full cell rotation  versus . The solid lines indicate power laws in .
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pcbi-1003967-g003: Swimming velocity versus sperm number.Rescaled swimming velocity plotted versus sperm number (double-logarithmic plot) for to two viscosity values (squares) and (triangles) given in MPCD units. Inset: Number of flagellar beats per full cell rotation versus . The solid lines indicate power laws in .

Mentions: The elongated model trypanosome can be regarded as a long slender body moving in a viscous fluid. For such an elastohydrodynamic system one expects a dimensionless parameter called the sperm number [33]–[35] to determine the complex propulsive dynamics of our model trypanosome [6]. The sperm number compares viscous to bending forces and is defined as , where is the elastohydrodynamic penetration length, the perpendicular friction coefficient per unit length, the bending rigidity of the cell body, and the angular frequency of the driving wave. In Fig. 3 we plot the rescaled swimming velocity as a function of for two sets of shear viscosity which approximately fall on the same master curve. Moreover, in the range from to , corresponding to an increase in frequency by a factor of 7, we approximately identify the scaling or as predicted in [36] and in agreement with Ref. [6]. For larger values of a second scaling regime occurs, which we attribute to the fact that the model trypanosome no longer swims in the quasi-static regime. The cell body rotates with an angular frequency . The number of flagellar beats per full rotation of the cell body, , roughly scales as (inset of Fig. 3) in agreement with Ref. [6]. Beyond the quasi-static regime we find . For , assumes the value , which matches the experimental value of measured in medium with the viscosity of blood [4]. For this the resulting dynamics of the cell shape and the swimming pattern of the model trypanosome closely resembles the real swimming trypanosome as demonstrated in S3 Video.


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 sperm number.Rescaled swimming velocity  plotted versus sperm number  (double-logarithmic plot) for to two viscosity values  (squares) and  (triangles) given in MPCD units. Inset: Number of flagellar beats per full cell rotation  versus . The solid lines indicate power laws in .
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003967-g003: Swimming velocity versus sperm number.Rescaled swimming velocity plotted versus sperm number (double-logarithmic plot) for to two viscosity values (squares) and (triangles) given in MPCD units. Inset: Number of flagellar beats per full cell rotation versus . The solid lines indicate power laws in .
Mentions: The elongated model trypanosome can be regarded as a long slender body moving in a viscous fluid. For such an elastohydrodynamic system one expects a dimensionless parameter called the sperm number [33]–[35] to determine the complex propulsive dynamics of our model trypanosome [6]. The sperm number compares viscous to bending forces and is defined as , where is the elastohydrodynamic penetration length, the perpendicular friction coefficient per unit length, the bending rigidity of the cell body, and the angular frequency of the driving wave. In Fig. 3 we plot the rescaled swimming velocity as a function of for two sets of shear viscosity which approximately fall on the same master curve. Moreover, in the range from to , corresponding to an increase in frequency by a factor of 7, we approximately identify the scaling or as predicted in [36] and in agreement with Ref. [6]. For larger values of a second scaling regime occurs, which we attribute to the fact that the model trypanosome no longer swims in the quasi-static regime. The cell body rotates with an angular frequency . The number of flagellar beats per full rotation of the cell body, , roughly scales as (inset of Fig. 3) in agreement with Ref. [6]. Beyond the quasi-static regime we find . For , assumes the value , which matches the experimental value of measured in medium with the viscosity of blood [4]. For this the resulting dynamics of the cell shape and the swimming pattern of the model trypanosome closely resembles the real swimming trypanosome as demonstrated in S3 Video.

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