scholarly journals Importance of erythrocyte deformability for the alignment of malaria parasite upon invasion

2019 ◽  
Author(s):  
S. Hillringhaus ◽  
G. Gompper ◽  
D. A. Fedosov
Keyword(s):  
Erythrocyte Membrane ◽  
Realistic Model ◽  
Attractive Potential ◽  
Adhesion Forces ◽  
Blood Diseases ◽  
Rbc Membrane ◽  
Erythrocyte Invasion ◽  
Adhesion Contact ◽  
Alignment Process ◽  
Membrane Deformations

ABSTRACTInvasion of erythrocytes by merozoites is an essential step for the survival and progression of malaria parasites. In order to invade red blood cells (RBCs), parasites have to adhere with their apex to the RBC membrane. Since a random adhesion contact between the parasite and membrane would be too inefficient, it has been hypothesized that merozoites are able to actively re-orient toward apex-membrane alignment. This is supported by several experimental observations which show that merozoites frequently induce considerable membrane deformations before the invasion process. Even though a positive correlation between RBC membrane deformation and successful invasion is established, the role of RBC mechanics and its deformation in the alignment process remains elusive. Using a mechanically realistic model of a deformable RBC, we investigate numerically the importance of RBC deformability for merozoite alignment. Adhesion between the parasite and RBC membrane is modeled by an attractive potential which might be inhomogeneous, mimicking possible adhesion gradients at the surface of a parasite. Our results show that RBC membrane deformations are crucial for successful merozoite alignment, and require strengths comparable to adhesion forces measured experimentally. Adhesion gradients along the parasite body further improve its alignment. Finally, an increased membrane rigidity is found to result in poor merozoite alignment, which can be a possible reason for the reduction in the invasion of RBCs in several blood diseases associated with membrane stiffening.STATEMENT OF SIGNIFICANCEPlasmodium parasites invade erythrocytes during the progression of malaria. To start invasion, the parasites have to re-orient themselves such that their apex establishes a direct contact with erythrocyte membrane. The re-orientation (or alignment) process is often associated with strong membrane deformations, which are believed to be induced by the parasite and are positively correlated with its alignment. We employ a mechanically realistic erythrocyte model to investigate the interplay of membrane deformations and merozoite alignment during parasite adhesion to an erythrocyte. Our model clearly demonstrates that erythrocyte membrane deformations are a key component of successful parasite alignment, since the re-orientation of parasites at rigidified membranes is generally poor. Therefore, our results suggest a possible mechanism for the reduction in erythrocyte invasion in several blood diseases associated with membrane stiffening.

scholarly journals Effect of malaria parasite shape on its alignment at erythrocyte membrane

2021 ◽  
Author(s):  
Anil K Dasanna ◽  
Sebastian Hillringhaus ◽  
Gerhard Gompper ◽  
Dmitry A Fedosov
Keyword(s):  
Spherical Shape ◽  
Coarse Grained ◽  
Local Curvature ◽  
Stochastic Nature ◽  
Rbc Membrane ◽  
Aspect Ratios ◽  
Strong Adhesion ◽  
Alignment Process ◽  
Pointed End ◽  
Membrane Deformations

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite's apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite's shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.

scholarly journals Effect of malaria parasite shape on its alignment at erythrocyte membrane

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anil K Dasanna ◽  
Sebastian Hillringhaus ◽  
Gerhard Gompper ◽  
Dmitry A Fedosov
Keyword(s):  
Spherical Shape ◽  
Coarse Grained ◽  
Local Curvature ◽  
Stochastic Nature ◽  
Rbc Membrane ◽  
Aspect Ratios ◽  
Strong Adhesion ◽  
Alignment Process ◽  
Pointed End ◽  
Membrane Deformations

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite's apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite's shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.

scholarly journals Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion

2020 ◽  
Author(s):  
Sebastian Hillringhaus ◽  
Anil K. Dasanna ◽  
Gerhard Gompper ◽  
Dmitry A. Fedosov
Keyword(s):  
Red Blood Cells ◽  
Erythrocyte Membrane ◽  
Blood Cells ◽  
Malaria Parasite ◽  
Invasion Process ◽  
Random Orientation ◽  
Hydrodynamic Simulations ◽  
Stochastic Nature ◽  
Rbc Membrane ◽  
Alignment Process

Malaria parasites invade healthy red blood cells (RBCs) during the blood stage of the disease. Even though parasites initially adhere to RBCs with a random orientation, they need to align their apex toward the membrane in order to start the invasion process. Using hydrodynamic simulations of a RBC and parasite, where both interact through discrete stochastic bonds, we show that parasite alignment is governed by the combination of RBC membrane deformability and dynamics of adhesion bonds. The stochastic nature of bond-based interactions facilitates a diffusive-like re-orientation of the parasite at the RBC membrane, while RBC deformation aids in the establishment of apexmembrane contact through partial parasite wrapping by the membrane. This bond-based model for parasite adhesion quantitatively captures alignment times measured experimentally and demonstrates that alignment times increase drastically with increasing rigidity of the RBC membrane. Our results suggest that the alignment process is mediated simply by passive parasite adhesion.

scholarly journals Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sebastian Hillringhaus ◽  
Anil K Dasanna ◽  
Gerhard Gompper ◽  
Dmitry A Fedosov
Keyword(s):  
Erythrocyte Membrane ◽  
Blood Cells ◽  
Malaria Parasite ◽  
Invasion Process ◽  
Random Orientation ◽  
Hydrodynamic Simulations ◽  
Stochastic Nature ◽  
Rbc Membrane ◽  
Alignment Process ◽  
Membrane Contact

Malaria parasites invade healthy red blood cells (RBCs) during the blood stage of the disease. Even though parasites initially adhere to RBCs with a random orientation, they need to align their apex toward the membrane in order to start the invasion process. Using hydrodynamic simulations of a RBC and parasite, where both interact through discrete stochastic bonds, we show that parasite alignment is governed by the combination of RBC membrane deformability and dynamics of adhesion bonds. The stochastic nature of bond-based interactions facilitates a diffusive-like re-orientation of the parasite at the RBC membrane, while RBC deformation aids in the establishment of apex-membrane contact through partial parasite wrapping by the membrane. This bond-based model for parasite adhesion quantitatively captures alignment times measured experimentally and demonstrates that alignment times increase drastically with increasing rigidity of the RBC membrane. Our results suggest that the alignment process is mediated simply by passive parasite adhesion.

Modeling the Effect of Surface Roughness on the Adhesion, Contact and Friction in Micro-Electro-Mechanical Systems (MEMS) Interfaces

2003 ◽  
Author(s):  
Noureddine Tayebi ◽  
Andreas A. Polycarpou
Keyword(s):  
Surface Texturing ◽  
Static Friction ◽  
Normal Operation ◽  
Root Mean Square Roughness ◽  
Adhesion Forces ◽  
Sensors And Actuators ◽  
Micro Electro Mechanical Systems ◽  
Friction Forces ◽  
Normal Forces ◽  
Adhesion Contact

It has been experimentally shown that surface texturing (roughening) decreases the effect of intermolecular adhesion forces that are significant in MEMS applications. These forces can hinder normal operation of sensors and actuators as well as micro-engines where they might increase friction, which could be catastrophic. In this paper, a model that predicts the effects of roughness, asymmetry, and flatness on the adhesion, contact, and friction forces in MEMS interfaces is presented. The three key parameters used to characterize the roughness the asymmetry and the flatness of a surface topography are the root-mean-square roughness (RMS), skewness and kurtosis, respectively. It is predicted that surfaces with high RMS, high kurtosis and positive skewness exhibit lower adhesion and static friction coefficient, even at extremely low external normal forces.

Modeling of Amorphous Carbon Overcoat for Investigation of Lubricant Transfer at the Head-Disk Interface

2014 ◽  
Author(s):  
Young Woo Seo ◽  
Frank E. Talke
Keyword(s):  
Hard Disk Drives ◽  
Intermolecular Forces ◽  
Realistic Model ◽  
Coarse Grained ◽  
Attractive Potential ◽  
Head Disk Interface ◽  
Carbon Overcoat ◽  
Lubricant Transfer ◽  
Disk Interface ◽  
Dynamics Simulations

In current hard disk drives, the spacing between the slider and the disk is reduced to the order of 1–2 nm. At such a narrow spacing, intermolecular forces at the head-disk interface play an important role in achieving a stable slider-disk interface. Even in the absence of actual head-disk contact, lubricant transfer between a slider and a disk may occur. Transferred lubricant can change the flying characteristics of the slider in subsequent read-write operations. It is therefore apparent that lubricant transfer at the head-disk interface is undesirable. In this paper, molecular dynamics simulations were performed to investigate lubricant transfer between a slider and a disk. A so-called coarse-grained bead spring (CGBS) model was implemented. In this model, the Lennard-Jones potential, the short-range polar attractive potential, and the finitely extensible nonlinear elastic potential functions were used to describe the intermolecular interactions at the head-disk interface. Also, in order to develop a realistic model of the carbon overcoat, different modeling approaches are discussed, including the use of rigid coarse-grained beads and a 3-body Tersoff potential function.

scholarly journals Delivery of the Malaria Virulence Protein PfEMP1 to the Erythrocyte Surface Requires Cholesterol-Rich Domains

2006 ◽  
Vol 5 (5) ◽  
pp. 849-860 ◽  
Author(s):  
Sarah Frankland ◽  
Akinola Adisa ◽  
Paul Horrocks ◽  
Theodore F. Taraschi ◽  
Timothy Schneider ◽  
...  
Keyword(s):  
Erythrocyte Membrane ◽  
Infected Erythrocyte ◽  
Membrane Microdomains ◽  
Human Malaria Parasite ◽  
Vesicle Budding ◽  
Erythrocyte Invasion ◽  
Major Virulence Factor ◽  
Erythrocyte Surface ◽  
Virulence Protein ◽  
Maurer's Clefts

ABSTRACT The particular virulence of the human malaria parasite Plasmodium falciparum derives from export of parasite-encoded proteins to the surface of the mature erythrocytes in which it resides. The mechanisms and machinery for the export of proteins to the erythrocyte membrane are largely unknown. In other eukaryotic cells, cholesterol-rich membrane microdomains or “rafts” have been shown to play an important role in the export of proteins to the cell surface. Our data suggest that depletion of cholesterol from the erythrocyte membrane with methyl-β-cyclodextrin significantly inhibits the delivery of the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). The trafficking defect appears to lie at the level of transfer of PfEMP1 from parasite-derived membranous structures within the infected erythrocyte cytoplasm, known as the Maurer's clefts, to the erythrocyte membrane. Thus our data suggest that delivery of this key cytoadherence-mediating protein to the host erythrocyte membrane involves insertion of PfEMP1 at cholesterol-rich microdomains. GTP-dependent vesicle budding and fusion events are also involved in many trafficking processes. To determine whether GTP-dependent events are involved in PfEMP1 trafficking, we have incorporated non-membrane-permeating GTP analogs inside resealed erythrocytes. Although these nonhydrolyzable GTP analogs reduced erythrocyte invasion efficiency and partially retarded growth of the intracellular parasite, they appeared to have little direct effect on PfEMP1 trafficking.

Characterisation of Plasmodium falciparum RESA-like protein peptides that bind specifically to erythrocytes and inhibit invasion

2007 ◽  
Vol 388 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Luis Eduardo Rodriguez ◽  
Ricardo Vera ◽  
John Valbuena ◽  
Hernando Curtidor ◽  
Javier Garcia ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Surface ◽  
Binding Assays ◽  
Gene Encoding ◽  
Trophozoite Stage ◽  
Rbc Membrane ◽  
Erythrocyte Invasion ◽  
Erythrocyte Surface ◽  
Maurer's Clefts

Abstract The Plasmodium falciparum ring-erythrocyte surface antigen (RESA)-like putative protein was identified and characterised. PCR and RT-PCR assays revealed that the gene encoding this protein was both present and being transcribed in P. falciparum strain FCB-2 16 h after erythrocyte invasion. Indirect immunofluorescence studies detected this protein in infected erythrocyte (IE) cytosol in dense fluorescent granules similar to Maurer's clefts at 16–20 h (parasites in ring and trophozoite stages) and very strongly on IE membranes at 22 h, suggesting that it is synthesised during early ring stages (16 h) and transported to the infected red blood cell (RBC) membrane surface during the trophozoite stage (22 h). Western blotting showed that antisera produced against polymerised synthetic peptides of this protein recognised a 72-kDa band in P. falciparum schizont lysate. P. falciparum RESA-like peptides used in normal RBC binding assays revealed that peptides 30326 (101NAEKI LGFDD KNILE ALDLFY120), 30334 (281RVTWK KLRTK MIKAL KKSLTY300) and 30342 (431SSPQR LKFTA GGGFC GKLRNY450) bind with high activity and saturability, presenting nM affinity constants. These peptides contain α-helical structural elements, as determined by circular dichroism, and inhibit P. falciparum in vitro invasion of normal RBCs by up to 91%, suggesting that some RESA-like protein regions are involved in intra-erythrocyte stage P. falciparum invasion.

Amount of cholesterol in host membrane affects erythrocyte invasion and replication by Babesia bovis

Parasitology ◽  
2006 ◽  
Vol 134 (5) ◽  
pp. 625-630 ◽  
Author(s):  
K. OKUBO ◽  
N. YOKOYAMA ◽  
N. TAKABATAKE ◽  
M. OKAMURA ◽  
I. IGARASHI
Keyword(s):  
Erythrocyte Membrane ◽  
Babesia Bovis ◽  
Cholesterol Depletion ◽  
Slight Reduction ◽  
Erythrocyte Invasion ◽  
Host Membrane ◽  
Growth Assay ◽  
Pre Treatment ◽  
Bovine Erythrocytes

SUMMARYCholesterol is a major component of the erythrocyte membrane. In the present study, we investigated the effects of cholesterol reduction in host bovine erythrocytes (RBC) on the growth of Babesia bovis, a major bovine haemoprotozoon. An in vitro growth assay with bovine RBC that had been prepared by pre-treatment with a cholesterol depletion agent (methyl-β-cyclodextrin, MCD) showed that the culture with 5 mm MCD-treated RBC inhibited the growth of B. bovis significantly as compared with that with the control RBC. In further experiments, the treatment with 5 mm MCD was proved to suppress both activities of the parasite, erythrocyte invasion and replication within the infected RBC. In contrast, a slight reduction in the membrane cholesterol by 1 mm MCD treatment promoted both their growth and erythrocyte invasion activity. These results indicate that erythrocyte invasion and replication by B. bovis are affected by the amount of cholesterol in the host erythrocyte membrane.

The Influence of Residual Stress on Micromachine Stiction

2004 ◽  
Author(s):  
Kai-Tak Wan ◽  
Lior Kogut
Keyword(s):  
Residual Stress ◽  
Residual Stresses ◽  
Microelectromechanical Systems ◽  
Adhesive Contact ◽  
Adhesion Forces ◽  
Adhesion Contact ◽  
Interfacial Contact ◽  
Cylindrical Punch ◽  
Punch Displacement

Adhesion plays an important role in microelectromechanical systems (MEMS). It is a major concern in MEMS reliability and oftentimes excessive adhesion forces lead to permanent adherence of MEMS surfaces resulting in microdevice failure. The role of residual stresses in the adhesive contact between a pre-stressed membrane and a rigid flat-ended cylindrical punch is studied. Breaking the contact can be achieved under either fixed-load or fixed-grips configuration. The influence of the residual stress on the pull-off force, punch displacement, and contact area at pull-off is studied. It is shown that residual stresses have significant influence on interfacial contact behavior in MEMS and, hence, should be taken into consideration in formulating the adhesion contact mechanics.

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