Biomembrane Function Research Articles

Comparison of structural effects of cholesterol, lanosterol, and oxysterol on phospholipid (POPC) bilayers

Membrane sterols contribute to the function of biomembranes by regulating the physical properties of the lipid bilayers. Cholesterol, a typical mammalian sterol, is biosynthesized by oxidation of lanosterol. From a molecular evolutionary perspective, lanosterol is considered the ancestral molecule of cholesterol. Here, we studied whether cholesterol is superior to lanosterol in regulating the physical properties of the lipid bilayer in terms of the structural effect on model biomembranes composed of a phospholipid. For comparison, oxysterol, which is formed by oxidation of cholesterol, was also studied. The phospholipid used was 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), which is abundantly found in mammalian biomembranes, and 7β-hydroxycholesterol, which is highly cytotoxic, was used as the oxysterol. The apparent molecular volume was calculated from the mass density determined by the flotation method using H2O and D2O, and the bilayer thickness was determined by reconstructing the electron density distribution from X-ray diffraction data of the POPC/sterol mixtures at a sterol concentration of 30 mol%. The apparent occupied area at the bilayer surface was calculated from the above two structural data. The cholesterol system had the thickest bilayer thickness and the smallest occupied area of the three sterols studied here. This indicates that the POPC/cholesterol bilayer has a better barrier property than the other two systems. Compared to cholesterol, the effects of lanosterol and 7β-hydroxycholesterol on lipid bilayer properties can be interpreted as suboptimal for the function of mammalian biomembranes.

The Nanometer-Scale Proximity of Bilayers Facilitates Intermembrane Lipid Transfer.

Biological membranes approach one another in various biological phenomena, such as lipid transport at membrane contact sites and membrane fusion. The proximity of two bilayers may cause environmental changes in the interbilayer space and alter the dynamics of lipid molecules. Here, we investigate the structure and dynamics of vesicles aggregated due to the depletion attraction caused by polyethylene glycol (PEG) through static and dynamic small-angle neutron scattering. Manipulation of the interbilayer distance using PEG-conjugated lipids reveals that lipid molecules rapidly transfer between vesicles when the opposing bilayers are within ∼2 nm of each other. This distance corresponds to a region in which water molecules are more structured than in bulk water. Kinetic analysis suggests that the decrease in water entropy is responsible for the progression of lipid transfer. These results provide a basis for understanding the dynamic function of biomembranes in confined regions.

Multi-View Kernel Sparse Representation for Identification of Membrane Protein Types.

Membrane proteins are the main undertaker of biomembrane functions and play a vital role in many biological activities of organisms. Prediction of membrane protein types has a great help in determining the function of proteins and understanding the interactions of membrane proteins. However, the biochemical experiment is expensive and not suitable for the large-scale identification of membrane protein types. Therefore, computational methods were used to improve the efficiency of biological experiments. Most existing computational methods only use a single feature of protein, or use multiple features but do not integrate these well. In our study, the protein sequence is described via three different views (features), including amino acid composition, evolutionary information and physicochemical properties of amino acids. To exploit information among all views (features), we introduce a coupling strategy for Kernel Sparse Representation based Classification (KSRC) and construct a new model called Multi-view KSRC (MvKSRC). We implement our method on 4 benchmark data sets of membrane proteins. The comparison results indicate that our method is much superior to all existing methods.

Cholesterol Stiffening of Lipid Membranes.

Biomembrane order, dynamics, and other essential physicochemical parameters are controlled by cholesterol, a major component of mammalian cell membranes. Although cholesterol is well known to exhibit a condensing effect on fluid lipid membranes, the extent of stiffening that occurs with different degrees of lipid acyl chain unsaturation remains an enigma. In this review, we show that cholesterol locally increases the bending rigidity of both unsaturated and saturated lipid membranes, suggesting there may be a length-scale dependence of the bending modulus. We review our published data that address the origin of the mechanical effects of cholesterol on unsaturated and polyunsaturated lipid membranes and their role in biomembrane functions. Through a combination of solid-state deuterium NMR spectroscopy and neutron spin-echo spectroscopy, we show that changes in molecular packing cause the universal effects of cholesterol on the membrane bending rigidity. Our findings have broad implications for the role of cholesterol in lipid–protein interactions as well as raft-like mixtures, drug delivery applications, and the effects of antimicrobial peptides on lipid membranes.Graphical

Micromechanics of Biomembranes.

Micromechanics techniques are playing an increasing role in characterization of biomembranes. The mechanical properties of membranes play an important role for a whole range of cellular processes. Lipid-protein biomembranes display lateral heterogeneity, domain formation, and morphological changes at mesoscopic and nanoscopic length scales. An attempt is made to introduce how membrane's material properties can be measured. Both fluctuation analysis and micro-pipette aspiration experiments have been used to quantify the micromechanics of membranes. The relationship between the structure and function of biomembranes is a critical concern in modern biology. This overview calls for a deeper understanding of how the cell complexity might be related to the mechanical properties of the lipid-protein membrane. Mechanical properties can influence cellular response to processes like adhesion, transport, differentiation, proliferation and migration.

Energetic and Structural Insights into Phospholipid Transfer from Membranes with Different Curvatures by Time-Resolved Neutron Scattering.

Understanding how lipid dynamics change with membrane curvature is important given that biological membranes constantly change their curvature and morphology through membrane fusion and endo-/exocytosis. Here, we used time-resolved small-angle neutron scattering and time-resolved fluorescence to characterize the properties and dynamics of phospholipids in vesicles with different curvatures. Dissociation of phospholipids from vesicles required traversing an energy barrier comprising positive enthalpy and negative entropy. However, lipids in membranes with high positive curvature have dense acyl chain packing and loose headgroup packing, leading to hydrophobic hydration due to water penetration into the membrane. These properties were found to lower the hydrophobic hydration enhancement associated with phospholipid dissociation and mitigate the acyl chain packing of lipids adjacent to the space created by the lipid dissociation, resulting in an increase in activation entropy. The results of this study provide important insights into the functions of biomembranes in relation to their dynamic structural changes.

Manifestation of oxidative stress during pregnancy in women with chronic diseases of hepatobiliary system against the background of reproductive losses

In the early stages of gestation the changes in the lipid peroxidation can lead to violations of regulatory and protective functions of biomembranes in pregnant women. The objective: to study the changes in the concentration of intermediate and final products of LPO during the first trimester of gestation in patients with early miscarriage against the background of chronic diseases of the hepatobiliary system. Materials and methods. 118 pregnant women in the first trimester of gestation (7-10 weeks), aged 22 - 39 y. o. (mean age 29.4 ± 2.7 years) have been examined.64 women (54.2%) were diagnosed with a risk of miscarriage, and 17 patients were diagnosed with involuntary miscarriage within 10-12 days. All women were diagnosed with non-viral and non-alcoholic chronic HBS paathology: hepatic steatosis had 38 patients (32.2%), 80 patients (67.8%) had non-alcoholic steatohepatitis; in 97 patients (82.2%) chronic non-calculous cholecystitis was diagnosed. The state of lipid peroxidation was assessed by the content of malonic dialdehyde spectrophotometrically, as well as diene conjugates in the blood The indicator of erythrocyte peroxide hemolysis was examined by the level of erythrocyte peroxide resistance. Results. A significant increase in intermediate and final products of lipid peroxidation in pregnant women with an unfavorable premorbid background in the form of chronic diseases of the hepatobiliary system and a history of reproductive losses. A significant increase of MDA and DC concentration was found at the risk of premature termination of pregnancy. The degree of PLO processes activation makes these parameters integrative criteria for the detection of systemic metabolic disorders during gestation in women with GBS extragenital pathology. Conclusion. During physiological pregnancy there is an accumulation of metabolites of lipid peroxidation, which is associated with an increase in basic metabolism in women and an increase in oxygen consumption from the blood.

Asymmetric desorption of lipid oxidation products induces membrane bending.

Lipid oxidation, detected in metabolic processes, is induced in excess when the cellular membrane suffers extra oxidative stress. Lipid oxidation can compromise biomembrane function in part through perturbations of lipid packing, membrane permeability, and morphology. Two major types of oxidation products, one with a partially truncated lipid tail with a hydrophilic group at the tail-end, and secondly, a lysolipid (with one of the chains completely truncated) can disturb the membrane bilayer packing significantly. However, they also have an increased tendency to desorb from the membrane. In this study we investigated desorption kinetics of two characteristic lipid oxidation products (PAzePC and 18 : 1 LysoPC) from a model membrane system, and we evaluated the consequences of this process on membrane shape transitions. Using a microfluidic chamber coupled with micropipette aspiration, we observed the incorporation of the two lipids into the membrane of a giant unilamellar vesicle (GUV) and further determined their desorption rates, association rates and flip-flop rates. For both lipids, the desorption is on the time scale of seconds, one to two orders of magnitude faster than their flipping rates. Dilution of the outer solution of the GUVs allowed asymmetric desorption of these two lipids from the GUVs. This process induced lipid number asymmetry and charge asymmetry, specifically for PAzePC containing GUVs, and caused membrane tubulation. Our results indicate that the desorption of lipid oxidation products can alter the local structure of biomembranes and result in morphological changes that may relate to membrane function.

Photoregulated "Breathing" Vesicle with Inversed Supramolecular Chirality.

Though phospholipids possess chiral centers, their chiral aggregation within bilayer cell membranes has seldom been referred and recognized. Insight into the chirality at higher levels in artificial molecular bilayer assemblies such as vesicles or liposomes is important to better understand biomembrane functions. In this work, we illustrate the fabrication of chiral vesicles with photoresponsive supramolecular chirality and structural transformation property. Cholesterol was conjugated to azobenzene via different spacers, of which molecular chirality underwent transfer to supramolecular level upon aggregation in water. The resultant building block self-assembled into unilamellar vesicles that could respond to light irradiation by showing reversible extension/contraction behavior. Such "breathing" behavior was accompanied with supramolecular chirality inversion from M- to P-handedness, confirmed by the solid-state crystal structure and electronic circular dichroism spectra based on density functional theory. The vesicle membrane behaves as a matrix to accommodate guest molecules via aromatic interactions, which significantly elevated the UV light resistance with respect to the structural and supramolecular chirality transformation. This work offers an unprecedented rational control over supramolecular chirality using photoresponsiveness in vesicular membranes.

Regularity for nonlinear elliptic equations and systems

We study the regularity of weak solutions to the elliptic system in divergence form divA( x , D u)=0 in an open set Ω of R n , n ≥2. The vector field A( x .ξ), A: Ω×R m×n →R m×n , has a variational nature in the sense that A( x ,ξ)= D ξ f ( x ,ξ), where f :Ω×R m×n →R is a convex Caratheodory integrand ; i.e., f = f ( x ,ξ) is measurable with respect to x ∈R n and it is a convex function with respect to ξ∈R m×n . If m =1 then the system reduces to a partial differential equation . In the context m >1 of general vector-valued maps and systems , a classical assumption finalized to the everywhere regularity of the weak solutions is a modulus-dependence in the energy integrand; i.e., we require that f ( x ,ξ)= g ( x ,|ξ|), where g :Ω×[0,∞)→[0,∞) is measurable with respect to x∈ R n and it is a convex and increasing function with respect to the gradient variable t∈[0,∞).

Coherent collective dynamics in phospholipid membranes: where are we now?

We review the main achievements accomplished in the study of the coherent collective dynamics of phospholipid membranes, i.e. , the collective vibrational excitations active on the sub-picoseconds to picoseconds time scale and terahertz frequencies, over a length scale comparable to the angstrom length scale. The first descriptions of the terahertz collective spectrum, mainly assigned to a single longitudinal acoustic-like mode similarly to simple liquids, have been progressively replaced by a complex scenario, with longitudinal and transverse acoustic-like and optic-like inelastic excitations. Complex phenomena (avoided crossing mechanisms between modes, a phonon gap introduced by the disorder and a slow- to fast-sound transition) have been highlighted in the dispersion curves of lipid bilayers. Systematic and comprehensive studies along the lines of the investigations reviewed here contribute to understand the role of the collective (coherent) chain dynamics in the passive transport across bilayers, in the formation of water wires inside dynamic defects in lipid bilayers and in other biological functions of biomembranes.

Scaling relationships for the elastic moduli and viscosity of mixed lipid membranes

The elastic and viscous properties of biological membranes play a vital role in controlling cell functions that require local reorganization of the membrane components as well as dramatic shape changes such as endocytosis, vesicular trafficking, and cell division. These properties are widely acknowledged to depend on the unique composition of lipids within the membrane, yet the effects of lipid mixing on the membrane biophysical properties remain poorly understood. Here, we present a comprehensive characterization of the structural, elastic, and viscous properties of fluid membranes composed of binary mixtures of lipids with different tail lengths. We show that the mixed lipid membrane properties are not simply additive quantities of the single-component analogs. Instead, the mixed membranes are more dynamic than either of their constituents, quantified as a decrease in their bending modulus, area compressibility modulus, and viscosity. While the enhanced dynamics are seemingly unexpected, we show that the measured moduli and viscosity for both the mixed and single-component bilayers all scale with the area per lipid and collapse onto respective master curves. This scaling links the increase in dynamics to mixing-induced changes in the lipid packing and membrane structure. More importantly, the results show that the membrane properties can be manipulated through lipid composition the same way bimodal blends of surfactants, liquid crystals, and polymers are used to engineer the mechanical properties of soft materials, with broad implications for understanding how lipid diversity relates to biomembrane function.

The role of polyunsaturated fatty acids (PUFA) in the formation of the structure and functions of biomembranes

Aim: To show the role of PUFA in the formation of biomembranes and to note the difference between ω-6 and ω-3 PUFA in action on the structure and some membrane functions.Methods: Analysis of the main publications on this issue over the past 10-15 years.Results: For the first time, a classification of fatty acids by their origin in the body, from various sources: microbes, plants, animals, is presented. The importance of the intake of long-chain PUFA (C20 and C22), the synthesis of which in the animal organism is limited, is emphasized. The direct effect of PUFA on membrane structures, which is not mediated by the products of their specific oxygenase oxidation, is shown.

The role of polyunsaturated fatty acids (PUFA) in the formation of the structure and functions of biomembranes

The role of polyunsaturated fatty acids (PUFA) in the formation of the structure and functions of biomembranes

High hydrostatic pressure treatment effects on selected tissue properties of fresh horticultural products

High hydrostatic pressure (HHP) treatments affect the integrity and function of biomembranes and proteins of fresh produces. Initially, pressure affects membrane permeability, directly linked to a reversible decline in cell turgor. Reversibility reflects the restoration of intracellular solute gradients by re-established membrane semi-permeability and functionality of membrane-bound proteins. Above a certain threshold, pressure effects become irreversible resulting in tissue damage. Combining cell pressure probe and tissue impedance measurements allows differentiation between reversible and irreversible effects. Thus, these parameters were comparatively investigated in both fresh red cabbage leaves and in radish tubers, species-specifically exposed to various pre-determined relevant HHP conditions (red cabbage: 150–200 MPa at 35–55 °C for 5–20 min; radish: 100–200 MPa, at 20–40 °C for 5–10 min). These specific treatments facilitated the evaluation of the transition between reversible changes in membrane and protein properties and irreversible damages. While turgor declined immediately after HHP treatments, tissue damage occurred only delayed. The two products differed in their responses to various HHP conditions. Generally, HHP effects were limited and reversible at (and certainly also below) 100 MPa but were amplified with intensity of pressure treatments. Industrial relevanceIncreasing food security aspects but also growing concerns against conventional thermal treatments demand the application of novel and gentle nonthermal hygienisation techniques such as high hydrostatic pressure (HHP) also for the production of fresh ready-to-eat salads. However, knowledge about potential impacts of different HHP ranges on metabolic functionality and freshness of fruits and vegetables, and thus produce quality, is still only sketchy.This study comprehensively differentiated the reversible and irreversible effects of processing conditions on the physiological and structural basis of HHP effects on fresh red cabbage leaves and radish tubers. It thus provides valuable information on the absolute limits of the applicability of HHP for safety of fresh produces. The fact that pressure treatments above 150 MPa always resulted in irreversible tissue damage indicated that even short-term HHP treatments at room temperature are not suitable for the gentle sanitation of perishable fresh produces but may probably be useful as quarantine measure against parasites and viruses.

Breakdown of the Coupling between the Lipid Membrane Dynamics of Differing Hierarchical Levels

Diverse biological functions of biomembranes are made possible by their rich dynamical behaviors across multiple scales. While the potential coupling between the dynamics of differing scales may underlie the machineries regulating the biomembrane-involving processes, the mechanism and even the existence of this coupling remains an open question, despite the latter being taken for granted. Via inelastic neutron scattering, we examined dynamics across multiple scales for the lipid membranes whose dynamic behaviors were perturbed by configurational changes at two membrane regions.

Uncoupling between the lipid membrane dynamics of differing hierarchical levels.

Diverse biological functions of biomembranes are made possible by their rich dynamic behaviors across multiple scales. While the potential coupling between the dynamics of differing scales may underlie the machineries regulating the biomembrane-involving processes, the mechanism and even the existence of this coupling remain an open question, despite the latter being taken for granted. Via inelastic neutron scattering, we examined dynamics across multiple scales for the lipid membranes whose dynamic behaviors were perturbed by configurational changes at two membrane regions. Surprisingly, the dynamic behavior of individual lipid molecules and their collective motions were not always coupled. This suggests that the expected causal relation between the dynamics of the differing hierarchical levels does not exist and that an apparent coupling can emerge by manipulating certain membrane configurations. The findings provide insight on biomembrane modeling and how cells might individually or concertedly control the multiscale membrane dynamics to regulate their functions.

A Mechanism of the Interaction of Metal Oxide Nanoparticles with Biological Membranes

Abstract—Advances in nanotechnologies and artificial methods for the synthesis of metal oxide nanoparticles with sizes of 1–100 nm raise the issue of their biological safety. Nanoparticles with a size of less than 10 nm are capable of penetrating into the bloodstream, followed by their entry into various organs, such as the brain, liver, kidneys, lungs, and spleen. Nanoparticles are a pathogenic exogenous factor that disturbs the structure and functions of natural biomembranes. We have previously shown using in vitro studies that nanoparticles with a diameter below a critical value of Rcr permeate the membrane. As a result, the microviscosity of the lipid bilayer of biomembranes decreases. This process is accompanied by the formation of through pores, which can combine into cracks and destroy the membrane. If the radius of the nanoparticles is greater than a critical value they are adsorbed on the membrane surface, thus increasing their microviscosity. In both cases, nanoparticles disrupt the normal functioning of natural biomembranes and cells. This paper presents a thermodynamic model of the direct (not due to endocytosis) penetration of nanoparticles into the lipid bilayer of the membrane. It has been shown that the Rcr value increases with an increase in the Zeta potential of the nanoparticles.

Lipidomic study of the influence of dietary fatty acids on structural lipids of cold-water nudibranch molluscs

Nudibranch molluscs occur in marine ecosystems worldwide and prey on numerous invertebrate species. During feeding, dietary fatty acids (FAs) unusual for nudibranchs are transferred to their lipids. Normal biomembrane functions require stable composition of structural polar lipids (PL), but the pathways of dietary FA utilization to PL in nudibranchs still remain unknown. A combination of chromatography and tandem high-resolution mass spectrometry was used to determine total lipid, PL, FA, and PL molecular species composition of two cold-water species of Dendronotus, which then were compared with those of Tritonia tetraquetra. The use of FA trophic markers showed that Dendronotus sp. and T. tetraquetra prey on different soft corals, while D. robustus may consumes hydrocorals and bryozoans. Nudibranch FA profiles were strongly modified by dietary FAs but their PL profilers were similar. Dietary FAs are not included in ceramide aminoethylphosphonate and inositol glycerophospholipids, but directed to ethanolamine, choline, and serine glycerophospholipids and, in some cases, form isobaric molecular species with different FA chain lengths. For such isobaric species, nudibranchs reduce the length of alkyl groups when very-long-chain FAs are obtained with diet. This molecular mechanism may explain the adaptation of nudibranch membrane structure to dietary input of unusual FAs.

The effect of high hydrostatic pressure acclimation on acute temperature tolerance and phospholipid fatty acid composition in the shallow-water shrimp Palaemon varians

Extant deep-sea fauna, including hydrothermal vent endemics such as bresiliid shrimp, are descended from shallow-water ancestors. Previous studies have demonstrated the capacity of shallow-water shrimp to acclimate to hydrostatic pressure representative of the vent environment. It has been proposed that this hyperbaric acclimation depends in part on shifts in phospholipid fatty acid composition to maintain biomembrane function. These shifts are also predicted to reduce critical temperature tolerance, potentially limiting the possibility of direct colonisation of the hydrothermal vent environment. Here, we present evidence that acclimation to high hydrostatic pressure (10 MPa ≈ 1000 m water depth) decreases acute temperature tolerance from 30.2 °C to 27.1 °C in the shallow-water shrimp Palaemon varians acclimated to 10 °C. Statistically significant shifts in phospholipid fatty acid composition occurred during exposure to high hydrostatic pressure, suggesting that homeoviscous modifications support shifts in environmental tolerances during hyperbaric acclimation. Despite the reduction in temperature tolerance, P. varians retains sufficient thermal scope to tolerate the thermal regime in the hydrothermal vent environment, allowing for the possibility of direct deep-sea hydrothermal vent colonisation by shallow-water shrimp.