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.

Modeling Diffusion and Vesiculation in Defective Human Erythrocyte Membrane

2013 ◽  
Author(s):  
He Li ◽  
George Lykotrafitis
Keyword(s):  
Lipid Bilayer ◽  
Hereditary Spherocytosis ◽  
Band 3 ◽  
Coarse Grained ◽  
Human Erythrocyte Membrane ◽  
The Past ◽  
Rbc Membrane ◽  
Proposed Model ◽  
Membrane Models ◽  
Membrane Vesiculation

The hemolytic disorders of hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) affect the lives of millions of individuals worldwide. In HS and HE, connections in the vertical and horizontal directions between components of the RBC membrane (see Fig. 1(a)), are disrupted due to defective proteins, leading to loss of the structural and functional integrity of the membrane (1–2). Moreover, disruptions of either the vertical interactions or horizontal interactions affect the lateral diffusivity of the mobile band 3 proteins, as the motion of band 3 in the RBC membrane is confined by the cytoskeleton (3). Although a number of coarse-grained molecular dynamics (CGMD) RBC membrane models have been developed in the past two decades, very few RBC membrane models have been used to study the disordered band 3 diffusion and membrane vesiculation in HS and HE. The implicit representations of either the lipid bilayer or the cytoskeleton in these membrane models limit their applications in the membrane instability problems in HS and HE. In this extended abstract, we develop a two-component CGMD human RBC membrane model that explicitly comprises both the lipid bilayer and the cytoskeleton. In this way, the interactions between the cytoskeleton and the proteins embedded in the lipid bilayer can be simulated. The proposed model allows us to measure the band 3 lateral mobility and simulate the process of membrane vesiculation in the membrane with protein defects.

scholarly journals Multiple stiffening effects of nanoscale knobs on human red blood cells infected with Plasmodium falciparum malaria parasite

2015 ◽  
Vol 112 (19) ◽  
pp. 6068-6073 ◽  
Author(s):  
Yao Zhang ◽  
Changjin Huang ◽  
Sangtae Kim ◽  
Mahdi Golkaram ◽  
Matthew W. A. Dixon ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Strain Hardening ◽  
Malaria Parasite ◽  
Molecular Mechanisms ◽  
Molecular Structures ◽  
Coarse Grained ◽  
Cell Stiffness ◽  
Rbc Membrane ◽  
Infected Rbcs ◽  
Spectrin Network

During its asexual development within the red blood cell (RBC), Plasmodium falciparum (Pf), the most virulent human malaria parasite, exports proteins that modify the host RBC membrane. The attendant increase in cell stiffness and cytoadherence leads to sequestration of infected RBCs in microvasculature, which enables the parasite to evade the spleen, and leads to organ dysfunction in severe cases of malaria. Despite progress in understanding malaria pathogenesis, the molecular mechanisms responsible for the dramatic loss of deformability of Pf-infected RBCs have remained elusive. By recourse to a coarse-grained (CG) model that captures the molecular structures of Pf-infected RBC membrane, here we show that nanoscale surface protrusions, known as “knobs,” introduce multiple stiffening mechanisms through composite strengthening, strain hardening, and knob density-dependent vertical coupling. On one hand, the knobs act as structural strengtheners for the spectrin network; on the other, the presence of knobs results in strain inhomogeneity in the spectrin network with elevated shear strain in the knob-free regions, which, given its strain-hardening property, effectively stiffens the network. From the trophozoite to the schizont stage that ensues within 24–48 h of parasite invasion into the RBC, the rise in the knob density results in the increased number of vertical constraints between the spectrin network and the lipid bilayer, which further stiffens the membrane. The shear moduli of Pf-infected RBCs predicted by the CG model at different stages of parasite maturation are in agreement with experimental results. In addition to providing a fundamental understanding of the stiffening mechanisms of Pf-infected RBCs, our simulation results suggest potential targets for antimalarial therapies.

scholarly journals New Approach In The Properties Evaluation Of Ultrafine-Grained OFHC Copper

2015 ◽  
Vol 60 (2) ◽  
pp. 605-614 ◽  
Author(s):  
T. Kvačkaj ◽  
A. Kováčová ◽  
J. Bidulská ◽  
R. Bidulský ◽  
R. Kočičko
Keyword(s):  
Mechanical Properties ◽  
Strain Rate ◽  
Tensile Tests ◽  
Coarse Grained ◽  
Wear Behaviour ◽  
Ofhc Copper ◽  
Strain Rates ◽  
Ultrafine Grained ◽  
Reduction Of Area ◽  
Pin On Disk

AbstractIn this study, static, dynamic and tribological properties of ultrafine-grained (UFG) oxygen-free high thermal conductivity (OFHC) copper were investigated in detail. In order to evaluate the mechanical behaviour at different strain rates, OFHC copper was tested using two devices resulting in static and dynamic regimes. Moreover, the copper was subjected to two different processing methods, which made possible to study the influence of structure. The study of strain rate and microstructure was focused on progress in the mechanical properties after tensile tests. It was found that the strain rate is an important parameter affecting mechanical properties of copper. The ultimate tensile strength increased with the strain rate increasing and this effect was more visible at high strain rates$({\dot \varepsilon} \sim 10^2 \;{\rm{s}}^{ - 1} )$. However, the reduction of area had a different progress depending on microstructural features of materials (coarse-grained vs. ultrafine-grained structure) and introduced strain rate conditions during plastic deformation (static vs. dynamic regime). The wear behaviour of copper was investigated through pin-on-disk tests. The wear tracks examination showed that the delamination and the mild oxidational wears are the main wear mechanisms.

Structural and Functional State of Erythrocyte Membranes at Drug Addiction

2021 ◽  
Vol 18 (1) ◽  
pp. 13-19
Author(s):  
A.I. Rabadanova ◽  
Keyword(s):  
Amino Acids ◽  
Drug Addiction ◽  
Functional State ◽  
Conformational Changes ◽  
Structural Integrity ◽  
Fluorescence Analysis ◽  
Heroin Addiction ◽  
Dimensional Structure ◽  
Erythrocyte Membranes ◽  
Drug Addicts

The steady growth in the number of drug addicts, especially among young people, dictates the need to find ways to prevent and treat this disease. In this regard, there is a need for a more detailed study of the mechanisms of the course of this disease using modern research methods, such as atomic force microscopy and fluorescence analysis of amino acid residues. Purpose of the work: to reveal the structural and functional state of erythrocyte membranes in drug addiction. Materials and methods. The studies were carried out on the erythrocyte membranes of 60 subjects suffering from heroin addiction. The shape and topography of the erythrocyte surface were studied, and spectral analysis of the proteins of the erythrocyte membranes was carried out. Results. The conducted AFM studies of erythrocyte membranes indicate the heterogeneity of the surface mechanical properties of the erythrocyte membranes of drug addicts. The data obtained indicate an acceleration of the aging process of erythrocytes in drug addiction, which goes in two ways: the formation of outgrowths on the plasmolemma, which subsequently die off (echinocytes) and invagination of the plasmolemma of erythrocytes (spherocytes). The fluorescence spectrum of amino acids in erythrocytes of drug addicts is characterized by a significant decrease in the intensity of almost all peaks and a shift of the fluorescence peak to the short-wave region. Findings. With drug addiction, changes in the structural integrity of red blood cells are noted. In people with drug addiction, in comparison with healthy people, there is a higher variability of the morphology of erythrocytes, which is expressed in a significant increase in the proportion of echinocytes and spherocytes against the background of a significant decrease in the number of discocytes. For the membrane proteins of erythrocytes of drug addicts, conformational changes are characteristic, manifested in a decrease in the intensity of fluorescence of aromatic amino acids, which indicates their structural modification and significant vulnerability of the hematopoietic system. They are largely determined by changes in the fluorescence intensity of tryptophan and, to a lesser extent, tyrosine, which indicates the preservation of the three-dimensional structure of the protein.

scholarly journals Lysophosphatidyl choline modulates mechanosensitive L-type Ca2+ current in circular smooth muscle cells from human jejunum

2009 ◽  
Vol 296 (4) ◽  
pp. G833-G839 ◽  
Author(s):  
Robert E. Kraichely ◽  
Peter R. Strege ◽  
Michael G. Sarr ◽  
Michael L. Kendrick ◽  
Gianrico Farrugia
Keyword(s):  
Shear Stress ◽  
Smooth Muscle ◽  
Lipid Bilayer ◽  
Stress Perfusion ◽  
Inactivation Kinetics ◽  
Circular Smooth Muscle ◽  
Lysophosphatidyl Choline ◽  
Membrane Stretch ◽  
Circular Layer ◽  
Patch Configuration

The L-type Ca2+ channel expressed in gastrointestinal smooth muscle is mechanosensitive. Direct membrane stretch and shear stress result in increased Ca2+ entry into the cell. The mechanism for mechanosensitivity is not known, and mechanosensitivity is not dependent on an intact cytoskeleton. The aim of this study was to determine whether L-type Ca2+ channel mechanosensitivity is dependent on tension in the lipid bilayer in human jejunal circular layer myocytes. Whole cell currents were recorded in the amphotericin-perforated-patch configuration, and lysophosphatidyl choline (LPC), lysophosphatidic acid (LPA), and choline were used to alter differentially the tension in the lipid bilayer. Shear stress (perfusion at 10 ml/min) was used to mechanostimulate L-type Ca2+ channels. The increase in L-type Ca2+ current induced by shear stress was greater in the presence of LPC (large head-to-tail proportions), but not LPA or choline, than in the control perfusion. The increased peak Ca2+ current also did not return to baseline levels as in control conditions. Furthermore, steady-state inactivation kinetics were altered in the presence of LPC, leading to a change in window current. These findings suggest that changes in tension in the plasmalemmal membrane can be transmitted to the mechanosensitive L-type Ca2+ channel, leading to altered activity and Ca2+ entry in the human jejunal circular layer myocyte.

scholarly journals Exaggerated cation leak from oxygenated sickle red blood cells during deformation: evidence for a unique leak pathway

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2374-2378
Author(s):  
T Sugihara ◽  
RP Hebbel
Keyword(s):  
Shear Stress ◽  
Lipid Hydroperoxide ◽  
Viscous Medium ◽  
Permeability Barrier ◽  
Biochemical Basis ◽  
Rbc Membrane ◽  
Gardos Channel ◽  
Ambient Oxygen ◽  
Applied Shear Stress ◽  
Leak Pathway

An abnormal susceptibility of the sickle red blood cell (RBC) membrane to deformation could compromise its permeability barrier function and contribute to the exuberant cation leakiness occurring during the sickling phenomenon. We examined this hypothesis by subjecting RBCs at ambient oxygen tension to elliptical deformation, applying shear stress in a viscous medium under physiologic conditions. Compared with normal and high-reticulocyte control RBCs, sickle RBCs manifest an exaggerated K leak response to deformation. This leak is fully reversible, is both Cl and Ca independent, and at pHe 7.4 is fully balanced so that Kefflux equals Nainflux. This abnormal susceptibility is also evident in that the K leak in response to deformation occurs at an applied shear stress of only 141 dyne/cm2 for sickle RBCs, as compared to 204 dyne/cm2 for normal RBCs. Fresh sickle RBC membranes contain elevated amounts of lipid hydroperoxide, the presence of which is believed to provide the biochemical basis for enhanced deformation susceptibility. When examined at pHe 6.8, oxygenated sickle RBCs acquire an additional, unbalanced (Kefflux > Nainflux) component to the K leak increment specifically ascribable to deformation. Studies with inhibitors suggest that this additional component is not caused by a known leak pathway (eg, either K:Cl cotransport or the Gardos channel). This abnormal susceptibility of the sickle membrane to development of cation leakiness during deformation probably contributes to the exuberant cation leak taking place during RBC sickling.

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.

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