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 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 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 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.

scholarly journals Why are SNAREpins rod-shaped?

2021 ◽  
Author(s):  
Jin Zeng ◽  
Zachary McDargh ◽  
Dong An ◽  
Ben O'Shaughnessy
Keyword(s):  
Membrane Fusion ◽  
Strong Support ◽  
Force Production ◽  
Snare Proteins ◽  
Coarse Grained ◽  
Aspect Ratios ◽  
Extended Contact ◽  
Fusion Site ◽  
Simple Body ◽  
Core Components

SNARE proteins are the core components of the cellular machineries that fuse membranes for neurotransmitter or hormone release and other fundamental processes. Fusion is accomplished when SNARE proteins hosted by apposing membranes form SNARE complexes called SNAREpins, but the mechanism of fusion remains unclear. Computational simulations of SNARE-mediated membrane fusion are challenging due to the millisecond timescales of physiological membrane fusion. Here we used ultra-coarse-grained (UCG) simulations to investigate the minimal requirements for a molecular intracellular fusogen, and to elucidate the mechanisms of SNARE-mediated fusion. We find fusion by simple body forces that push vesicles together is highly inefficient. Inter-vesicle fusogens with different aspect ratios can fuse vesicles only if they are rodlike, of sufficient length to clear the fusogens from the fusion site by entropic forces. Simulations with rod-shaped SNAREpin-like fusogens fused 50-nm vesicles on ms timescales, driven by entropic forces along a reproducible fusion pathway. SNARE-SNARE and SNARE-membrane entropic forces cleared the fusion site and pressed the vesicles into an extended contact zone (ECZ), drove stalk nucleation at the high curvature ECZ boundary, and expanded the stalk into a long-lived hemifusion diaphragm in which a simple pore completed fusion. Our results provide strong support for the entropic hypothesis of SNARE-mediated membrane fusion, and implicate the rodlike structure of the SNAREpin complex as a necessity for entropic force production and fusion.

Molecular simulation of diffusion mechanism of nanorods in cross-linked network

Nanoscale ◽  
2021 ◽  
Author(s):  
Bo-Ran Zhao ◽  
Bin Li ◽  
Xinghua Shi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Simulation ◽  
Diffusion Mechanism ◽  
Coarse Grained ◽  
Aspect Ratios ◽  
Coarse Grained Molecular Dynamics

We study the diffusion of rod-shape nanocarriers with different rigidities and aspect ratios in cross-linked network using coarse-grained molecular dynamics (CGMD) simulations. The diffusivities of nanorods increase as the reduction...

MOCVD Copper Metallization for High Aspect Ratios TSV 3D Integration.

2018 ◽  
Vol 2018 (1) ◽  
pp. 000718-000727 ◽  
Author(s):  
Sabrina Fadloun ◽  
Dean Stephens ◽  
Patrice Gergaud ◽  
Elisabeth Blanquet ◽  
Thierry Mourier ◽  
...  
Keyword(s):  
Seed Layer ◽  
Copper Film ◽  
Chemical Vapor ◽  
Copper Metallization ◽  
Organic Chemical ◽  
Aspect Ratios ◽  
Organometallic Precursor ◽  
Strong Adhesion ◽  
Metal Organic ◽  
Copper Seed Layer

Abstract MOCVD (Metal-Organic Chemical Vapor Deposition) copper metallization was developed on 300mm wafers, to fulfil 3D Through-Silicon Via (TSV) interconnect requirements. Using a fluorine-free organometallic precursor, the bis(dimethylamino-2-propoxy)copper (II) Cu[OCHMeCH2NMe2]2 at low temperature deposition, we developed a high purity, low stress copper film with strong adhesion to a TiN barrier layer. Argon was used as a carrier gas and H2 and/or H2O as a co-reactant. This MOCVD technique offers good conformality observed with 10μm×120μmTSVs. The thin copper seed layer was successfully integrated on 300mm wafers. A new XRD protocol was developed to characterize the copper seed layer along the TSV sidewalls, revealed higher microstructure quality, lower stressed in the case of copper film deposited by CVD compared to those deposited by i-PVD.

scholarly journals Coupled elasticity–diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles

2015 ◽  
Vol 12 (102) ◽  
pp. 20141023 ◽  
Author(s):  
Jizeng Wang ◽  
Long Li
Keyword(s):  
Diffusion Model ◽  
Cellular Uptake ◽  
Configurational Entropy ◽  
Host Cells ◽  
Target Cells ◽  
Animal Cells ◽  
Dynamic Simulations ◽  
Aspect Ratios ◽  
Dynamics Simulations ◽  
Membrane Deformations

Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity–diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand–receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand–receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake.

scholarly journals Deconvolution of Ferromagnetic Resonance Spectrum of Magnetic Nanoparticle Assembly Using Genetic Algorithm

2021 ◽  
Author(s):  
N. A. Usov ◽  
O. N. Serebryakova
Keyword(s):  
Genetic Algorithm ◽  
Magnetic Anisotropy ◽  
Ferromagnetic Resonance ◽  
Magnetite Nanoparticles ◽  
Magnetic Moments ◽  
Spherical Shape ◽  
Thermal Fluctuations ◽  
Nanoparticle Assembly ◽  
Aspect Ratios ◽  
Exciting Frequency

Abstract The ferromagnetic resonance (FMR) spectra of dilute random assemblies of magnetite nanoparticles with cubic magnetic anisotropy and various aspect ratios are calculated using the stochastic Landau-Lifshitz equation at a finite temperature, T = 300 K, taking into account the thermal fluctuations of the particle magnetic moments. Particles of non-spherical shape in the first approximation are described as elongated spheroids with a given semiaxes ratio a/b, where a and b are the long and transverse semiaxes of a spheroid, respectively. A representative database of FMR spectra is created for assemblies of randomly oriented spheroidal magnetite nanoparticles with various transverse diameters D = 5 - 25 nm, moderate aspect ratios a/b = 1.0 - 1.8, and magnetic damping constants k = 0.1, 0.2. The basic FMR spectra of assemblies with D = 25 nm at different aspect ratios can be considered as representatives of assemblies of single-domain magnetite nanoparticles with transverse diameters D > 25 nm. The database is calculated at exciting frequency f = 4.9 GHz (S-band) to clarify clearly the details of the FMR spectrum that depend on the nature of the particle magnetic anisotropy. The data obtained make it possible to analyze arbitrary combined FMR spectra constructed as weighted linear combinations of FMR spectra of the base assemblies. In addition, using a genetic algorithm, the corresponding inverse problem is solved. The latter consists in determining the volume fractions of the base assemblies in some arbitrary nanoparticle assembly, which is represented by its FMR spectrum.PACS: 75.20.-g; 75.50.Tt; 75.40.Mg

Two-Component Coarse-Grain Model for Erythrocyte Membrane

2011 ◽  
Author(s):  
George Lykotrafitis ◽  
He Li
Keyword(s):  
Shear Stress ◽  
Lipid Bilayer ◽  
Structural Integrity ◽  
Finite Difference Methods ◽  
Coarse Grained ◽  
Erythrocyte Membranes ◽  
Strain Rates ◽  
Rbc Membrane ◽  
Linear Behavior ◽  
Spectrin Network

Biological membranes are vital components of living cells as they function to maintain the structural integrity of the cells. Red blood cell (RBC) membrane comprises the lipid bilayer and the cytoskeleton network. The lipid bilayer consists of phospholipids, integral membrane proteins, peripheral proteins and cholesterol. It behaves as a 2D fluid. The cytoskeleton is a network of spectrin tetramers linked at the actin junctions. It is connected to the lipid bilayer primarily via Band-3 and ankyrin proteins. In this paper, we introduce a coarse-grained model with high computational efficiency for simulating a variety of dynamic and topological problems involving erythrocyte membranes. Coarse-grained agents are used to represent a cluster of lipid molecules and proteins with a diameter on the order of lipid bilayer thickness and carry both translational and rotational freedom. The membrane cytoskeleton is modeled as a canonical exagonal network of entropic springs that behave as Worm-Like-Chains (WLC). By simultaneously invoking these characteristics, the proposed model facilitates simulations that span large length-scales (∼ μm) and time-scales (∼ ms). The behavior of the model under shearing at different rates is studied. At low strain rates, the resulted shear stress is mainly due to the spectrin network and it shows the characteristic non-linear behavior of entropic networks, while the viscosity of the fluid-like lipid bilayer contributes to the resulting shear stress at higher strain rates. The apparent ease of this model in combining the spectrin network with the lipid bilayer presents a major advantage over conventional continuum methods such as finite element or finite difference methods for cell membranes.

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