scholarly journals Cyclic mechanical stresses alter erythrocyte membrane composition and microstructure and trigger macrophage phagocytosis

2021 ◽  
Author(s):  
Antoni Garcia-Herreros ◽  
Yi-Ting Yeh ◽  
Zhangli Peng ◽  
Juan C. del Álamo
Keyword(s):  
Cell Metabolism ◽  
Membrane Vesicles ◽  
Mechanical Stresses ◽  
Cell Aging ◽  
Membrane Composition ◽  
Biophysical Properties ◽  
Proteomics Analysis ◽  
Blood Flows ◽  
Membrane Cytoskeleton ◽  
Macrophage Phagocytosis

AbstractRed blood cells (RBCs) are cleared from the circulation when they become damaged or display aging signals targeted by macrophages. This process occurs mainly in the spleen, where blood flows through submicrometric constrictions called inter-endothelial slits (IES), subjecting RBCs to large-amplitude deformations. In this work, we circulated RBCs through microfluidic devices containing microchannels that replicate the IES. The cyclic mechanical stresses experienced by the cells affected their biophysical properties and molecular composition, accelerating cell aging. Specifically, RBCs quickly transitioned to a more spherical, less deformable phenotype that hindered microchannel passage, causing hemolysis. This transition was associated with the release of membrane vesicles, which self-extinguished as the spacing between membrane-cytoskeleton linkers became tighter. Proteomics analysis of the mechanically aged RBCs revealed significant losses of essential proteins involved in antioxidant protection, gas transport, and cell metabolism. Finally, we show that these changes made mechanically aged RBCs more susceptible to macrophage phagocytosis. These results provide a comprehensive model to explain how physical stress induces RBC clearance in the spleen.

scholarly journals Osmotic stress and vesiculation as key mechanisms controlling bacterial sensitivity and resistance to TiO2 nanoparticles

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Christophe Pagnout ◽  
Angelina Razafitianamaharavo ◽  
Bénédicte Sohm ◽  
Céline Caillet ◽  
Audrey Beaussart ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Osmotic Stress ◽  
Inner Core ◽  
Metal Oxide Nanoparticles ◽  
Membrane Vesicles ◽  
Outer Core ◽  
Membrane Composition ◽  
Cell Turgor ◽  
Bacterial Sensitivity ◽  
Membrane Components

AbstractToxicity mechanisms of metal oxide nanoparticles towards bacteria and underlying roles of membrane composition are still debated. Herein, the response of lipopolysaccharide-truncated Escherichia coli K12 mutants to TiO2 nanoparticles (TiO2NPs, exposure in dark) is addressed at the molecular, single cell, and population levels by transcriptomics, fluorescence assays, cell nanomechanics and electrohydrodynamics. We show that outer core-free lipopolysaccharides featuring intact inner core increase cell sensitivity to TiO2NPs. TiO2NPs operate as membrane strippers, which induce osmotic stress, inactivate cell osmoregulation and initiate lipid peroxidation, which ultimately leads to genesis of membrane vesicles. In itself, truncation of lipopolysaccharide inner core triggers membrane permeabilization/depolarization, lipid peroxidation and hypervesiculation. In turn, it favors the regulation of TiO2NP-mediated changes in cell Turgor stress and leads to efficient vesicle-facilitated release of damaged membrane components. Remarkably, vesicles further act as electrostatic baits for TiO2NPs, thereby mitigating TiO2NPs toxicity. Altogether, we highlight antagonistic lipopolysaccharide-dependent bacterial responses to nanoparticles and we show that the destabilized membrane can generate unexpected resistance phenotype.

Role of HBV Replication in Host Cell Metabolism: A Proteomics Analysis

2013 ◽  
Vol 10 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Laleh Sadrolodabaee ◽  
Tiong Low ◽  
Huixing Feng ◽  
Wei Chen
Keyword(s):  
Host Cell ◽  
Cell Metabolism ◽  
Proteomics Analysis ◽  
Hbv Replication

scholarly journals Impact of nanoscale hindrances on the relationship between lipid packing and diffusion in model membranes

2020 ◽  
Author(s):  
Daniel Beckers ◽  
Dunja Urbancic ◽  
Erdinc Sezgin
Keyword(s):  
Plasma Membrane ◽  
Cell Biology ◽  
Membrane Vesicles ◽  
Theoretical Models ◽  
Correlation Spectroscopy ◽  
Suitable Model ◽  
Biophysical Properties ◽  
Plasma Membrane Vesicles ◽  
Free Standing ◽  
Lipid Packing

AbstractMembrane models have allowed for precise study of the plasma membrane’s biophysical properties, helping to unravel both structural and dynamic motifs within cell biology. Free standing and supported bilayer systems are popular models to reconstitute the membrane related processes. Although it is well-known that each have their advantages and limitations, comprehensive comparison of their biophysical properties is still lacking. Here, we compare the diffusion and lipid packing in giant unilamellar vesicles, planar and spherical supported membranes and cell-derived giant plasma membrane vesicles. We apply florescence correlation spectroscopy, spectral imaging and super-resolution STED-FCS to study the diffusivity, lipid packing and nanoscale architecture of these membrane systems, respectively. Our data show that lipid packing and diffusivity is tightly correlated in free-standing bilayers. However, nanoscale interactions in the supported bilayers cause deviation from this correlation. This data is essential to develop accurate theoretical models of the plasma membrane and will serve as a guideline for suitable model selection in future studies to reconstitute biological processes.

scholarly journals Aberrant Membrane Composition and Biophysical Properties Impair Erythrocyte Morphology and Functionality in Elliptocytosis

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1120
Author(s):  
Hélène Pollet ◽  
Anne-Sophie Cloos ◽  
Amaury Stommen ◽  
Juliette Vanderroost ◽  
Louise Conrard ◽  
...  
Keyword(s):  
Cholesterol Content ◽  
Membrane Curvature ◽  
Acid Sphingomyelinase ◽  
Cholesterol Depletion ◽  
Membrane Composition ◽  
Biophysical Properties ◽  
Erythrocyte Morphology ◽  
Lipid Domain ◽  
Functional Consequences

Red blood cell (RBC) deformability is altered in inherited RBC disorders but the mechanism behind this is poorly understood. Here, we explored the molecular, biophysical, morphological, and functional consequences of α-spectrin mutations in a patient with hereditary elliptocytosis (pEl) almost exclusively expressing the Pro260 variant of SPTA1 and her mother (pElm), heterozygous for this mutation. At the molecular level, the pEI RBC proteome was globally preserved but spectrin density at cell edges was increased. Decreased phosphatidylserine vs. increased lysophosphatidylserine species, and enhanced lipid peroxidation, methemoglobin, and plasma acid sphingomyelinase (aSMase) activity were observed. At the biophysical level, although membrane transversal asymmetry was preserved, curvature at RBC edges and rigidity were increased. Lipid domains were altered for membrane:cytoskeleton anchorage, cholesterol content and response to Ca2+ exchange stimulation. At the morphological and functional levels, pEl RBCs exhibited reduced size and circularity, increased fragility and impaired membrane Ca2+ exchanges. The contribution of increased membrane curvature to the pEl phenotype was shown by mechanistic experiments in healthy RBCs upon lysophosphatidylserine membrane insertion. The role of lipid domain defects was proved by cholesterol depletion and aSMase inhibition in pEl. The data indicate that aberrant membrane content and biophysical properties alter pEl RBC morphology and functionality.

Differences in L-alanine uptake by livers of Wistar and lean Zucker rats

1991 ◽  
Vol 11 (2) ◽  
pp. 85-93
Author(s):  
B. Ruiz ◽  
J. Casado ◽  
M. Pastor-Anglada ◽  
A. Felipe
Keyword(s):  
Plasma Membrane ◽  
Wistar Rats ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Zucker Rats ◽  
Plasma Membrane Vesicles ◽  
Blood Flows ◽  
Old Rats ◽  
Lower Capacity

The L-alanine uptake by livers of Wistar and lean Zucker rats has been studied. The hepatic uptake and fractional extraction rates of alanine were estimated in 50–55 day old rats. No significant differences in amino acid concentrations and blood flows in afferent and efferent liver vessels were seen in lean Zucker rats when compared with Wistar rats. However, the hepatic uptake (1.6±0.1 and 0.7±0.1 μmol/min/100 g bw, p<0.01) and the fractional extraction (26.8±2.1 and 15.2±3.1%, p<0.05) were much lower in Zucker than in Wistar rats. The hepatic active transport of L-alanine was determined in vitro using isolated plasma membrane vesicles. Vesicles isolated from livers of lean Zucker rats showed similar values of Km (2.5±0.7 vs 2.0±0.5 mM for Wistar and Zucker respectively, N.S.), but lower values of Vmax when compared with Wistar rats (1.1±0.1 vs 0.6±0.005 nmol/mg prot 5 s, p<0.01, for Wistar and lean Zucker rats respectively). These results indicate that, the liver of lean Zucker rats concentrates alanine less efficiently than the liver of Wistar rats. This fact correlates well with a lower capacity of the Na+-dependent L-alanine trasport in liver plasma membrane vesicles from lean Zucker rats.

scholarly journals Ion channels can be allosterically regulated by membrane domains near a de-mixing critical point

2018 ◽  
Vol 150 (12) ◽  
pp. 1769-1777 ◽  
Author(s):  
Ofer Kimchi ◽  
Sarah L. Veatch ◽  
Benjamin B. Machta
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Ising Model ◽  
Critical Point ◽  
Membrane Vesicles ◽  
Membrane Properties ◽  
Membrane Composition ◽  
Plasma Membrane Vesicles ◽  
Liquid Phases ◽  
Markovian Dynamics

Ion channels are embedded in the plasma membrane, a compositionally diverse two-dimensional liquid that has the potential to exert profound influence on their function. Recent experiments suggest that this membrane is poised close to an Ising critical point, below which cell-derived plasma membrane vesicles phase separate into coexisting liquid phases. Related critical points have long been the focus of study in simplified physical systems, but their potential roles in biological function have been underexplored. Here we apply both exact and stochastic techniques to the lattice Ising model to study several ramifications of proximity to criticality for idealized lattice channels, whose function is coupled through boundary interactions to critical fluctuations of membrane composition. Because of diverging susceptibilities of system properties to thermodynamic parameters near a critical point, such a lattice channel’s activity becomes strongly influenced by perturbations that affect the critical temperature of the underlying Ising model. In addition, its kinetics acquire a range of time scales from its surrounding membrane, naturally leading to non-Markovian dynamics. Our model may help to unify existing experimental results relating the effects of small-molecule perturbations on membrane properties and ion channel function. We also suggest ways in which the role of this mechanism in regulating real ion channels and other membrane-bound proteins could be tested in the future.

Active urea transport and an unusual basolateral membrane composition in the gills of a marine elasmobranch

2001 ◽  
Vol 280 (1) ◽  
pp. R16-R24 ◽  
Author(s):  
Glenn A. Fines ◽  
James S. Ballantyne ◽  
Patricia A. Wright
Keyword(s):  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Structural Features ◽  
The Body ◽  
Squalus Acanthias ◽  
Phospholipid Bilayer ◽  
Molar Ratio ◽  
Maximal Velocity ◽  
Urea Transport ◽  
Membrane Composition

In elasmobranch fishes, urea occurs at high concentrations (350–600 mM) in the body fluids and tissues, where it plays an important role in osmoregulation. Retention of urea by the gill against this huge blood-to-water diffusion gradient requires specialized adaptations to the epithelial cell membranes. Experiments were performed to determine the mechanisms and structural features that facilitate urea retention by the gill of the spiny dogfish Squalus acanthias. Analysis of urea uptake by gill basolateral membrane vesicles revealed the presence of a phloretin-sensitive (half inhibition 0.09 mM), sodium-coupled, secondary active urea transporter (Michaelis constant = 10.1 mM, maximal velocity = 0.34 μmol · h−1 · mg protein−1). We propose that this system actively transports urea out of the gill epithelial cells back into the blood against the urea concentration gradient. Lipid analyses of the basolateral membrane revealed high levels of cholesterol contributing to the highest reported cholesterol-to-phospholipid molar ratio (3.68). This unique combination of active urea transport and modification of the phospholipid bilayer membrane is responsible for decreasing the gill permeability to urea and facilitating urea retention by the gill of Squalus acanthias.

scholarly journals A Genetic Titration of Membrane Composition in C. elegans Reveals its Importance for Multiple Cellular and Physiological Traits

Genetics ◽  
2021 ◽  
Author(s):  
Ranjan Devkota ◽  
Delaney Kaper ◽  
Rakesh Bodhicharla ◽  
Marcus Henricsson ◽  
Jan Borén ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fluorescence Recovery After Photobleaching ◽  
Saturated Fatty Acids ◽  
Physiological Traits ◽  
Membrane Composition ◽  
Wild Type ◽  
Biophysical Properties ◽  
C Elegans ◽  
Different Temperatures ◽  
Proper Functions

Abstract The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five C. elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262);paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14);nhr-49(et8), and mdt-15(et14);nhr-49(et8);acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluid gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.

scholarly journals A Disposable Blood-on-a-Chip for Simultaneous Measurement of Multiple Biophysical Properties

Micromachines ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 475 ◽  
Author(s):  
Yang Kang
Keyword(s):  
Microfluidic Device ◽  
Vascular Diseases ◽  
Blood Flow Rate ◽  
Biophysical Properties ◽  
Autologous Plasma ◽  
Aggregation Index ◽  
Blood Flows ◽  
Rbc Aggregation ◽  
Biophysical Indices ◽  
Rbc Deformability

Biophysical properties are widely used to detect pathophysiological processes of vascular diseases or clinical states. For early detection of cardiovascular diseases, it is necessary to simultaneously measure multiple biophysical properties in a microfluidic environment. However, a microfluidic-based technique for measuring multiple biophysical properties has not been demonstrated. In this study, a simple measurement method was suggested to quantify three biophysical properties of blood, including red blood cell (RBC) deformability, RBC aggregation, and hematocrit. To demonstrate the suggested method, a microfluidic device was constructed, being composed of a big-sized channel (BC), a parallel micropillar (MP), a main channel, a branch channel, inlet, and outlets. By operating a single syringe pump, blood was supplied into the inlet of the microfluidic device, at a periodic on-off profile (i.e., period = 240 s). The RBC deformability index (DI) was obtained by analyzing the averaged blood velocity in the branch channel. Additionally, the RBC aggregation index (AIN) and the hematocrit index (HiBC) were measured by analyzing the image intensity of blood flows in the MP and the BC, respectively. The corresponding contributions of three influencing factors, including the turn-on time (Ton), the amplitude of blood flow rate (Q0), and the hematocrit (Hct) on the biophysical indices (DI, AIN, and HiBC) were evaluated quantitatively. As the three biophysical indices varied significantly with respect to the three factors, the following conditions (i.e., Ton = 210 s, Q0 = 1 mL/h, and Hct = 50%) were maintained for consistent measurement of biophysical properties. The proposed method was employed to detect variations of biophysical properties depending on the concentrations of autologous plasma, homogeneous hardened RBCs, and heterogeneous hardened RBCs. Based on the observations, the proposed method exhibited significant differences in biophysical properties depending on base solutions, homogeneous hardened RBCs (i.e., all RBCs fixed with the same concentration of glutaraldehyde solution), and heterogeneous hardened RBCs (i.e., partially mixed with normal RBCs and homogeneous hardened RBCs). Additionally, the suggested indices (i.e., DI, AIN, and HiBC) were effectively employed to quantify three biophysical properties, including RBC deformability, RBC aggregation, and hematocrit.

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