Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion
- Theoretical Physics of Living Matter, Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, Germany
Figures
Figure 1
Sketch of parasite and RBC models.
(a) Two-dimensional sketch of a parasite with a directional vector from the parasite’s back at to its apex at . (b) Three-dimensional triangulated surfaces of a RBC (red) and a parasite …
Figure 2
Calibration of parasite adhesion parameters.
(a) A time instance of parasite motion at RBC membrane from an experimental video (Weiss et al., 2015) (top) and simulation (bottom), see also Video 1. To obtain the distribution of merozoite …
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Figure 2—source data 1
Source data for graphs shown in Figure 2(b,c).
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig2-data1-v2.zip
Figure 3 with 1 supplement
Parasite adhesion to a deformable RBC.
(a) Sketch of apex distance and alignment angle . The apex distance is defined as a distance (magenta line) between the parasite’s apex and the closest vertex of RBC membrane. The alignment …
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Figure 3—source data 1
Source data for graphs shown in Figure 3b,c and Figure 3—figure supplement 1.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig3-data1-v2.zip
Figure 3—figure supplement 1
Parasite adhesion to a rigid RBC (see section ‘Effect of RBC rigidity’).
Probability distributions of (a) the apex distance , and (b) the alignment angle . The dashed line in the apex distance distribution indicates the cutoff of repulsive LJ interactions.
Figure 4
Comparison of alignment times obtained from direct DPD simulations and MC sampling.
(a) Two-dimensional probability map as a function of and . Each bin represents a single alignment state and the color corresponds to probability of that state. The dark green area ( and , …
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Figure 4—source data 1
Source data for graphs shown in Figure 4a–c.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig4-data1-v2.zip
Figure 5 with 2 supplements
Variations in stretching and bending energies, the number of bonds , the head distance , and the alignment angle as a function of time for the default parameter set given in Table 2.
Temporal changes in the number of bonds are shown for both long and short bond types. The dashed lines in the bottom plot correspond to the alignment criteria in Equation 4. For all quantities, the …
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Figure 5—source data 1
Source data for graphs shown in Figure 5 and Figure 5—figure supplements 1 and 2.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig5-data1-v2.zip
Figure 5—figure supplement 1
Dependence of parasite wrapping on the position at RBC membrane.
(a) Average total number of bonds between the merozoite and RBC as a function of the distance between their centers of mass. (b) Illustration of parasite adhesion at the RBC rim (marked by I) and …
Figure 5—figure supplement 2
Different alignment characteristics, including (a) deformation energy, (b) number of bonds, (c) apex distance, (d) alignment angle, and (e) fixed-time displacement, for several values of parameter which determines the effective membrane thickness.
Figure 6 with 1 supplement
Effect of the off-rate on (a) the parasite’s fixed-time displacement, (b) RBC deformation energy, and (c) alignment time.
Since the off-rate controls the lifetime of bonds, a smaller off-rate results in a stronger adhesion, a lower parasite displacement, and a faster alignment time.
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Figure 6—source data 1
Source data for graphs shown in Figure 6a–c and Figure 6—figure supplement 1.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig6-data1-v2.zip
Figure 6—figure supplement 1
Effect of the off-rate on (a) the apex distance, (b) alignment angle, and (c) the number of bonds.
Figure 7 with 1 supplement
Effect of the extensional bond rigidities on parasite alignment.
(a) RBC deformation energy and (b) the number of short and long bonds as a function of . corresponds to the reference case with parameters given in Table 2. Note that both and are changed …
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Figure 7—source data 1
Source data for graphs shown in Figure 7a,b and Figure 7—figure supplement 1.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig7-data1-v2.zip
Figure 7—figure supplement 1
Effect of the extensional bond rigidities on (a) the apex distance, (b) alignment angle, and (c) fixed-time displacement of the parasite.
Figure 8 with 2 supplements
Effect of the density of long ligands on parasite alignment.
(a) Number of short and long bonds and (b) parasite alignment times as a function of . Note that remains constant in all simulations. Here, the bond kinetic rates are , , and . In case of …
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Figure 8—source data 1
Source data for graphs shown in Figure 8a,b and Figure 8—figure supplements 1 and 2.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig8-data1-v2.zip
Figure 8—figure supplement 1
Effect of the density of long ligands on (a) deformation energy, (b) fixed-time displacement, (c) apex distance, and (d) alignment angle.
Figure 8—figure supplement 2
Alignment results of simulations with only long ligands, i.e. for .
(a) Deformation energy, (b) the number of bonds, (c) apex distance, (d) alignment angle, and (e) fixed-time displacement of the merozoite for the three cases: (1) and , (2) and (the …
Figure 9
Effect of RBC membrane rigidity on (a) alignment time and (b) parasite fixed-time displacement for different off-rates .
Note that for a rigid RBC with , parasite alignment time could not be computed through the MC sampling, as the alignment criteria have never been met in direct simulations.
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Figure 9—source data 1
Source data for graphs shown in Figure 9a,b.
- https://cdn.elifesciences.org/articles/56500/elife-56500-fig9-data1-v2.zip
Videos
Video 1
Parasite motion at the membrane of a deformable RBC for the reference RBC-parasite interactions from Table 2.
. See Figure 2a.
Video 2
Parasite adhesion and dynamics on a deformable RBC for a reduced off-rate .
.
Video 3
Parasite dynamics at the surface of a rigid RBC for the reference RBC-parasite interactions from Table 2.
.
Tables
Table 1
Simulation parameters given in both model and physical units.
The effective RBC diameter sets a basic length, the thermal energy defines an energy scale, and RBC relaxation time sets a time scale in the simulated system, where is the RBC surface …
| Parameter | Simulation value | Physical value |
|---|---|---|
| 133.5 | ||
| 0.01 | ||
| 0.92 s | ||
| 1.85 | ||
| µ | ||
| 1230 | ||
| 3000 | ||
Table 2
List of bond parameters that are used to calibrate displacement of the parasite at the RBC membrane in simulations (see Video 1) against available experimental data (Weiss et al., 2015), as shown in Figure 2b.
The parameter values in simulations are given in terms of the length scale , energy scale , and timescale . The densities of long and short ligands are given in terms of parasite vertex …
| Parameter | Simulation value | Physical value |
|---|---|---|
| 0.4 | ||
| 0.6 | ||
