Lung surfactant protein SP-B promotes formation of bilayer reservoirs from monolayer and lipid transfer between the interface and subphase

We investigated the possible role of SP-B proteins in the function of lung surfactant. To this end, lipid monolayers at the air/water interface, bilayers in water, and transformations between them in the presence of SP-B were simulated. The proteins attached bilayers to monolayers, providing close proximity of the reservoirs with the interface. In the attached aggregates, SP-B mediated establishment of the lipid-lined connection similar to the hemifusion stalk. Via this connection, a lipid flow was initiated between the monolayer at the interface and the bilayer in water in a surface-tension-dependent manner. On interface expansion, the flow of lipids to the monolayer restored the surface tension to the equilibrium spreading value. SP-B induced formation of bilayer folds from the monolayer at positive surface tensions below the equilibrium. In the absence of proteins, lipid monolayers were stable at these conditions. Fold nucleation was initiated by SP-B from the liquid-expanded monolayer phase by local bending, and the proteins lined the curved perimeter of the growing fold. No effect on the liquid-condensed phase was observed. Covalently linked dimers resulted in faster kinetics for monolayer folding. The simulation results are in line with existing hypotheses on SP-B activity in lung surfactant and explain its molecular mechanism.     

Dermaseptin 01 as antimicrobial peptide with rich biotechnological potential: study of peptide interaction with membranes containing Leishmania amazonensis lipid‐rich extract and membrane models

This article addresses the interactions of the synthetic antimicrobial peptide dermaseptin 01 (GLWSTIKQKGKEAAIAAA‐ KAAGQAALGAL‐NH₂, DS 01) with phospholipid (PL) monolayers comprising (i) a lipid‐rich extract of Leishmania amazonensis (LRE‐La), (ii) zwitterionic PL (dipalmitoylphosphatidylcholine, DPPC), and (iii) negatively charged PL (dipalmitoylphosphatidylglycerol, DPPG). The degree of interaction of DS 01 with the different biomembrane models was quantified from equilibrium and dynamic liquid‐air interface parameters. At low peptide concentrations, interactions between DS 01 and zwitterionic PL, as well as with the LRE‐La monolayers were very weak, whereas with negatively charged PLs the interactions were stronger. For peptide concentrations above 1 µg/ml, a considerable expansion of negatively charged monolayers occurred. In the case of DPPC, it was possible to return to the original lipid area in the condensed phase, suggesting that the peptide was expelled from the monolayer. However, in the case of DPPG, the average area per lipid molecule in the presence of DS 01 was higher than pure PLs even at high surface pressures, suggesting that at least part of DS 01 remained incorporated in the monolayer. For the LRE‐La monolayers, DS 01 also remained in the monolayer. This is the first report on the antiparasitic activity of AMPs using Langmuir monolayers of a natural lipid extract from L. amazonensis. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Heat shock protein 70 is translocated to lipid droplets in rat adipocytes upon heat stimulation

In mammalian cells, lipid storage droplets contain a triacylglycerol and cholesterol ester core surrounded by a phospholipid monolayer into which a number of proteins are imbedded. These proteins are thought to be involved in modulating the formation and metabolic functions of the lipid droplet. In this study, we show that heat stress upregulates several heat shock proteins (Hsps), including Hsp27, Hsp60, Hsp70, Hsp90, and Grp78, in primary and differentiated adipocytes. Immunostaining and immunoblotting data indicate that among the Hsps examined, only Hsp70 is induced to redirect to the lipid droplet surface in heat-stressed adipocytes. The thermal induction of Hsp70 translocation to lipid droplet does not typically happen in a temperature- or time-dependent manner and occurs abruptly at 30-40 min and rapidly achieves a steady state within 60 min after 40 degrees C stress of adipocytes. Though Hsp70 is co-localized with perilipin on the lipid droplets in stressed adipocytes, immunoprecipitation experiments suggest that Hsp70 does not directly interact with perilipin. Alkaline treatments indicate that Hsp70 associates with the droplet surface through non-hydrophobic interactions. We speculate that Hsp70 might noncovalently associate with monolayer microdomains of the lipid droplet in a manner similar to its interaction with lipid bilayer moieties composed of specific fatty acids. As an acute and specific cellular response to the heat stimulation, accumulation of Hsp70 on adipocytes lipid droplets might be involved in stabilizing the droplet monolayer, transferring nascent proteins to the lipid droplets, or chaperoning denatured proteins on the droplet for subsequent refolding.     

Lateral tensions and pressures in membranes and lipid monolayers

The effects of lateral tension on the properties of membranes are often explained in comparison with analogous experiments on monolayers, which yield more detailed data. To calculate the effects of changes in tension on the composition of, or incorporation of amphiphiles into membranes we examine (i) the fidelity of the monolayer analogy, (ii) the range of possible tensions in a membrane, and the way in which tensions arise and (iii) the equilibrium partitioning of amphiphiles between aqueous solution and a bilayer under tension. We argue that, at the same areas per molecule, a monolayer at an $\text{n-}\text{alkane}\text{/}\text{water}$ interface is a closer analogy of the lipid bilayer than a monolayer at an air/water interface. Next, we show from a thermodynamic argument that changes in membrane tension can affect the absorption of very large amphiphiles such as proteins, but that physiological tensions are unlikely to affect the absorption of lipids or drugs. Finally we consider the possibility that the measured bulk tension in a complicated membrane such as that of the erythrocyte may be larger than the local tension in the fluid mosaic portions, and suggest a model which explains the ability of the erythrocyte membrane to withstand much higher tensions than other biological membranes and lipid bilayers.     

An Asymmetry in Monolayer Tension Regulates Lipid Droplet Budding Direction

Cells store excess energy in the form of neutral lipids that are synthesized and encapsulated within the endoplasmic reticulum intermonolayer space. The lipids next demix to form lipid droplets (LDs), which, surprisingly, bud off mostly toward the cytosol. This directional LD formation is critical to energy metabolism, but its mechanism remains poorly understood. Here, we reconstituted the LD formation topology by embedding artificial LDs into the intermonolayer space of bilayer vesicles. We provide experimental evidence that the droplet behavior in the membrane is recapitulated by the physics of three-phase wetting systems, dictated by the equilibrium of surface tensions. We thereupon determined that slight tension asymmetries between the membrane monolayers regulate the droplet budding side. A differential regulation of lipid or protein composition around a forming LD can generate a monolayer tension asymmetry that will determine the LD budding side. Our results offer, to our knowledge, new insights on how the proteins might regulate LD formation side by generating a monolayer tension asymmetry.     

Decoding P4-ATPase substrate interactions

Cellular membranes display a diversity of functions that are conferred by the unique composition and organization of their proteins and lipids. One important aspect of lipid organization is the asymmetric distribution of phospholipids (PLs) across the plasma membrane. The unequal distribution of key PLs between the cytofacial and exofacial leaflets of the bilayer creates physical surface tension that can be used to bend the membrane; and like Ca²⁺, a chemical gradient that can be used to transduce biochemical signals. PL flippases in the type IV P-type ATPase (P4-ATPase) family are the principle transporters used to set and repair this PL gradient and the asymmetric organization of these membranes are encoded by the substrate specificity of these enzymes. Thus, understanding the mechanisms of P4-ATPase substrate specificity will help reveal their role in membrane organization and cell biology. Further, decoding the structural determinants of substrate specificity provides investigators the opportunity to mutationally tune this specificity to explore the role of particular PL substrates in P4-ATPase cellular functions. This work reviews the role of P4-ATPases in membrane biology, presents our current understanding of P4-ATPase substrate specificity, and discusses how these fundamental aspects of P4-ATPase enzymology may be used to enhance our knowledge of cellular membrane biology.     

The Surface and Hydration Properties of Lipid Droplets

Lipid droplets (LDs) are energy storage organelles composed of neutral lipids, such as triacylglycerol (TG) and sterol esters, surrounded by a phospholipid (PL) monolayer. Their central role in metabolism, complex life cycle, and unique lipid monolayer surface have garnered great attention over the last decade. In this article, results from the largest and longest all-atom simulations to date suggest that 5–8% of the LD surface is occupied by TG molecules, a number that exceeds the maximal solubility reported for TGs in PL bilayers (2.8%). Two distinct classes of TG molecules that interact with the LD monolayer are found. Those at the monolayer surface (SURF-TG) are ordered like PLs with the glycerol moiety exposed to water, creating a significant amount of chemically unique packing defects, and the acyl chains extended toward the LD center. In contrast, the TGs that intercalate just into the PL tail region (CORE-TG) are disordered and increase the amount of PL packing defects and the PL tail order. The degree of interdigitation caused by CORE-TG is stable and determines the width of the TG-PL overlap, whereas that caused by SURF-TG fluctuates and is highly correlated with the area per PL or the expansion of the monolayer. Thus, when the supply of PLs is limited, SURF-TG may reduce surface tension by behaving as a secondary membrane component. The hydration properties of the simulated LD systems demonstrate ∼10 times more water in the LD core than previously reported. Collectively, the reported surface and hydration properties are expected to play a direct role in the mechanisms by which proteins target and interact with LDs.     

Phase behavior of lipid bilayers under tension

Given the proposed importance of membrane tension in regulating cellular functions, we explore the effects of a finite surface tension on phase equilibrium using a molecular theory that captures the quantitative structure of the phase diagram of the tensionless DPPC/DOPC/Cholesterol lipid bilayer. We find that an increase in the surface tension decreases the temperature of the transition from liquid to gel in a pure DPPC system by ～1.0 K/(mN/m), and decreases the liquid-disordered to liquid-ordered transition at constant chemical potentials by approximately the same amount. Our results quantitatively isolate the role of tension in comparison to other thermodynamic factors, such as pressure, in determining the phase behavior of lipid bilayers.     

Monolayers at the oil/water interface as a proper model for bilayer membranes

In order to clarify the structural relationship between lipid monolayer and bilayer membranes, physical states of these membranes are discussed from their energetic points of view. It is concluded that the monolayer formed at the oil/water interface is a proper model system to represent the physical state of half of a bilayer in its liquid crystalline state. The theoretical prediction is confirmed by the monolayer surface tension measurements and the bilayer conductance experiments with water soluble (extrinsic) proteins. It is also deduced that the surface pressure of the bilayer in the liquid crystalline state is quite high, about 45 dyn/cm, and the interaction of cytochrome c with the bilayer is mainly electrostatic at the bilayer membrane periphery.     

A molecular dynamics study of the response of lipid bilayers and monolayers to trehalose

Surface tensions evaluated from molecular dynamics simulations of fully hydrated dipalmitoylphosphatidylcholine bilayers and monolayers at surface areas/lipid of 54, 64, and 80 A2 are uniformly lowered 4-8 dyn/cm upon addition of trehalose in a 1:2 trehalose/lipid ratio. Constant surface tension simulations of bilayers yield the complementary result: an increase in surface area consistent with the surface pressure-surface area (pi-A) isotherms. Hydrogen bonding by trehalose, replacement of waters in the headgroup region, and modulation of the dipole potential are all similar in bilayers and monolayers at the same surface area. These results strongly support the assumption that experimental measurements on the interactions of surface active components such as trehalose with monolayers can yield quantitative insight to their effects on bilayers. The simulations also indicate that the 20-30 dyn/cm difference in surface tension of the bilayer leaflet and monolayer arises from differences in the chain regions, not the headgroup/water interfaces.     

A modified squeeze-out mechanism for generating high surface pressures with pulmonary surfactant

The exact mechanism by which pulmonary surfactant films reach the very low surface tensions required to stabilize the alveoli at end expiration remains uncertain. We utilized the nanoscale sensitivity of atomic force microscopy (AFM) to examine phospholipid (PL) phase transition and multilayer formation for two Langmuir-Blodgett (LB) systems: a simple 3 PL surfactant-like mixture and the more complex bovine lipid extract surfactant (BLES). AFM height images demonstrated that both systems develop two types of liquid condensed (LC) domains (micro- and nano-sized) within a liquid expanded phase (LE). The 3 PL mixture failed to form significant multilayers at high surface pressure (π while BLES forms an extensive network of multilayer structures containing up to three bilayers. A close examination of the progression of multilayer formation reveals that multilayers start to form at the edge of the solid-like LC domains and also in the fluid-like LE phase. We used the elemental analysis capability of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to show that multilayer structures are enriched in unsaturated PLs while the saturated PLs are concentrated in the remaining interfacial monolayer. This supports a modified squeeze-out model where film compression results in the hydrophobic surfactant protein-dependent formation of unsaturated PL-rich multilayers which remain functionally associated with a monolayer enriched in disaturated PL species. This allows the surface film to attain low surface tensions during compression and maintain values near equilibrium during expansion.     

How cholesterol is distributed between monolayers in asymmetric lipid membranes

The distribution of cholesterol in asymmetric lipid bilayers was studied by extensive coarse-grained molecular dynamics simulations. The effects of the lipid head group charge, acyl chain saturation, spontaneous membrane curvature and surface tension of the membrane were investigated. Four asymmetric bilayers containing DOPC, DOPS, DSPC or DSPS lipids were simulated on a time scale extended to tens of microseconds. We show that cholesterol strongly prefers anionic lipids to neutral and saturated lipid tails to unsaturated with a distribution ratio of ~0.7 in neutral/anionic bilayers and of ~0.4 in unsaturated/saturated bilayers. Multiple flip-flop transitions of cholesterol were observed directly, and their mean times ranged from 80 to 250?ns. It was shown that the distribution of cholesterol in the asymmetric membrane depends not only on the type of lipid, but also on the local membrane curvature and the surface tension. The membrane curvature enhances the influence of the lipid head groups on cholesterol distribution, while non-optimal surface tension caused by different areas per lipid in different monolayers increases the effect of the lipid tail saturation. It was clearly seen that the monolayers of asymmetric bilayers are interdependent. Mean distances from the bilayer center to cholesterol molecules depend not only on the type of the lipid in the considered monolayer but also on the composition of the opposite monolayer.     

E. coli Outer Membrane and Interactions with OmpLA

The outer membrane of Gram-negative bacteria is a unique asymmetric lipid bilayer composed of phospholipids (PLs) in the inner leaflet and lipopolysaccharides (LPSs) in the outer leaflet. Its function as a selective barrier is crucial for the survival of bacteria in many distinct environments, and it also renders Gram-negative bacteria more resistant to antibiotics than their Gram-positive counterparts. Here, we report the structural properties of a model of the Escherichia coli outer membrane and its interaction with outer membrane phospholipase A (OmpLA) utilizing molecular dynamics simulations. Our results reveal that given the lipid composition used here, the hydrophobic thickness of the outer membrane is ∼3 Å thinner than the corresponding PL bilayer, mainly because of the thinner LPS leaflet. Further thinning in the vicinity of OmpLA is observed due to hydrophobic matching. The particular shape of the OmpLA barrel induces various interactions between LPS and PL leaflets, resulting in asymmetric thinning around the protein. The interaction between OmpLA extracellular loops and LPS (headgroups and core oligosaccharides) stabilizes the loop conformation with reduced dynamics, which leads to secondary structure variation and loop displacement compared to that in a DLPC bilayer. In addition, we demonstrate that the LPS/PL ratios in asymmetric bilayers can be reliably estimated by the per-lipid surface area of each lipid type, and there is no statistical difference in the overall membrane structure for the outer membranes with one more or less LPS in the outer leaflet, although individual lipid properties vary slightly.     

Comparison of double layer potentials in lipid monolayers and lipid bilayer membranes

Summary It is shown that the Gouy-Chapman double layer analysis adequately describes the variation of the surface potential of monolayers of acidic natural lipids over a wide range of surface charge density and salt concentration. It is also shown that the potential which initially appears when an electrolyte gradient is rapidly imposed across a bilayer membrane is due to a difference in the double layer potentials on the two sides of the membrane. This conclusion follows from the fact that the observed bilayer potentials arise much more rapidly than can be accounted for by charge migration across the membrane and from the observation that the bilayer membrane concentration potentials, when measured immediately after establishment of a gradient, are equal to the surface potential change observed when the subphase concentration of a monolayer of the same lipid is changed by an amount equal to the gradient across the bilayer. The bilayer potential and monolayer potential changes, so measured, agree in a number of different electrolyte solutions over a wide range of electrolyte concentrations and surface charge densities. Because of this agreement and the applicability of the Gouy theory to monolayers, initial bilayer potentials may be calculated if the composition of the mixture used to form the membrane is known, provided that the pK's and areas of such components are available. In the absence of this information, membrane potentials may be calculated from electrophoretic data on the membrane lipid mixture; the conditions under which the latter approach is possible have been determined. The experimental results indicate that the composition of monolyers and bilayers spread from the same lipid mixture in decane are very similar, that the composition of the two types of film closely resembles the composition of the solution used to generate them, and that bilayer membranes are close-packed. The evidence further indicates that if any hydrocarbon solvent remains in these bilayers, it must be so situated that it contributes little, if anything, to the surface area. The steady state potential in the bilayer membrane system is frequently not identical with the initial potential which supports the hypothesis that in many cases only a fraction of the electrical conductance of unmodified membranes is caused by the ions which constitute the bulk electrolyte. An expression for the relationship between diffusion and double layer potentials has been derived which shows that, in the absence of any intrinsic selectivity of the hydrocarbon region of the membrane for hydrogen, hydroxyl, or impurity, the two potentials should be identical.     

The influence of dioxan on the bilayer and monolayer phase transition of phospholipids

The influence of 1.4.-dioxan on the bilayer phase transition of various phospholipids was studied by differential scanning calorimetry and turbidity measurements. The addition of 1.4.-dioxan to lipid bilayers decreases the transition temperature T_m increases the transition enthalpy of the transition. The cooperativity of the transition is unaffected. The phospholipid monolayer transition from the liquid-condensed to the liquid-expanded phase was measured by recording area versus temperature curves at constant surface pressure (isobars). The monolayer transition temperature at constant surface pressure is increased when 1.4.-dioxan is added to the subphase. The change in molecular area becomes larger. A comparison of monolayer isobars on water and water/dioxan as subphase at constant surface tension rather than surface pressure leads to a decrease of the transition temperature on water/dioxan as subphase. This decrease as well as the larger change in molecular area at the monolayer transition can be correlated to the decrease in T_m and the increase in the transition enthalpy of the corresponding bilayer system. 1.4.-Dioxan seems to accumulate at the lipid head group/water interface, thus lowering the tension of the bilayer membrane. This cyclic ether can be used for altering the characteristics of bilayer membranes without disturbing the lipid chain organization.     

Kinematics,material symmetry,and energy densities for lipid bilayers with spontaneous curvature

Continuum mechanical tools are used to describe the deformation, energy density, and material symmetry of a lipid bilayer with spontaneous curvature. In contrast to conventional approaches in which lipid bilayers are modeled by material surfaces, here we rely on a three-dimensional approach in which a lipid bilayer is modeling by a shell-like body with finite thickness. In this setting, the interface between the leaflets of a lipid bilayer is assumed to coincide with the mid-surface of the corresponding shell-like body. The three-dimensional deformation gradient is found to involve the curvature tensors of the mid-surface in the spontaneous and the deformed states, the deformation gradient of the mid-surface, and the transverse deformation. Attention is also given to the coherency of the leaflets and to the area compatibility of the closed lipid bilayers (i.e., vesicles). A hyperelastic constitutive theory for lipid bilayers in the liquid phase is developed. In combination, the requirements of frame indifference and material symmetry yield a representation for the energy density of a lipid bilayer. This representation shows that three scalar invariants suffice to describe the constitutive response of a lipid bilayer exhibiting in-plane fluidity and transverse isotropy. In addition to exploring the geometrical and physical properties of these invariants, fundamental constitutively associated kinematical quantities are emphasized. On this basis, the effect on the energy density of assuming that the lipid bilayer is incompressible is considered. Lastly, a dimension reduction argument is used to extract an areal energy density per unit area from the three-dimensional energy density. This step explains the origin of spontaneous curvature in the areal energy density. Importantly, along with a standard contribution associated with the natural curvature of the lipid bilayer, our analysis indicates that constitutive asymmetry between the leaflets of the lipid bilayer gives rise to a secondary contribution to the spontaneous curvature.     

E.?coli Outer Membrane and Interactions with OmpLA

The outer membrane of Gram-negative bacteria is a unique asymmetric lipid bilayer composed of phospholipids (PLs) in the inner leaflet and lipopolysaccharides (LPSs) in the outer leaflet. Its function as a selective barrier is crucial for the survival of bacteria in many distinct environments, and it also renders Gram-negative bacteria more resistant to antibiotics than their Gram-positive counterparts. Here, we report the structural properties of a model of the Escherichia coli outer membrane and its interaction with outer membrane phospholipase A (OmpLA) utilizing molecular dynamics simulations. Our results reveal that given the lipid composition used here, the hydrophobic thickness of the outer membrane is ∼3 Å thinner than the corresponding PL bilayer, mainly because of the thinner LPS leaflet. Further thinning in the vicinity of OmpLA is observed due to hydrophobic matching. The particular shape of the OmpLA barrel induces various interactions between LPS and PL leaflets, resulting in asymmetric thinning around the protein. The interaction between OmpLA extracellular loops and LPS (headgroups and core oligosaccharides) stabilizes the loop conformation with reduced dynamics, which leads to secondary structure variation and loop displacement compared to that in a DLPC bilayer. In addition, we demonstrate that the LPS/PL ratios in asymmetric bilayers can be reliably estimated by the per-lipid surface area of each lipid type, and there is no statistical difference in the overall membrane structure for the outer membranes with one more or less LPS in the outer leaflet, although individual lipid properties vary slightly.     

Theoretical analysis of hydrophobic matching and membrane-mediated interactions in lipid bilayers containing gramicidin.

We present a quantitative analysis of the effects of hydrophobic matching and membrane-mediated protein-protein interactions exhibited by gramicidin embedded in dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC) bilayers (Harroun et al., 1999. Biophys. J. 76:937-945). Incorporating gramicidin, at 1:10 peptide/lipid molar ratio, decreases the phosphate-to-phosphate (PtP) peak separation in the DMPC bilayer from 35.3 A without gramicidin to 32.7 A. In contrast, the same molar ratio of gramicidin in DLPC increases the PtP from 30.8 A to 32.1 A. Concurrently, x-ray in-plane scattering showed that the most probable nearest-neighbor separation between gramicidin channels was 26.8 A in DLPC, but reduced to 23.3 A in DMPC. In this paper we review the idea of hydrophobic matching in which the lipid bilayer deforms to match the hydrophobic surface of the embedded proteins. We use a simple elasticity theory, including thickness compression, tension, and splay terms to describe the membrane deformation. The energy of membrane deformation is compared with the energy cost of hydrophobic mismatch. We discuss the boundary conditions between a gramicidin channel and the lipid bilayer. We used a numerical method to solve the problem of membrane deformation profile in the presence of a high density of gramicidin channels and ran computer simulations of 81 gramicidin channels to find the equilibrium distributions of the channels in the plane of the bilayer. The simulations contain four parameters: bilayer thickness compressibility 1/B, bilayer bending rigidity Kc, the channel-bilayer mismatch Do, and the slope of the interface at the lipid-protein boundary s. B, Kc, and Do were experimentally measured; the only free parameter is s. The value of s is determined by the requirement that the theory produces the experimental values of bilayer thinning by gramicidin and the shift in the peak position of the in-plane scattering due to membrane-mediated channel-channel interactions. We show that both hydrophobic matching and membrane-mediated interactions can be understood by the simple elasticity theory.     

Investigation of phospholipid area compression induced by calcium-mediated dextran sulfate interaction.

The association of anionic polyelectrolytes such as dextran sulfate (DS) to zwitterionic phospholipid surfaces via Ca(2+) bridges results in a perturbation of lipid packing at physiologically relevant Ca(2+) concentrations. Lipid area compression was investigated in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) multilamellar bilayer dispersions by (2)H-NMR and in monolayer studies. Binding of DS to DMPC surfaces via Ca(2+) results in denser lipid packing, as indicated by higher lipid chain order. DMPC order parameters are homogeneously increased throughout the lipid bilayer. Higher order translates into more extended hydrocarbon chains and decreased average lipid area per molecule. Area compression is reported as a function of DS concentration and molecular weight. Altering the NaCl and Ca(2+) concentrations modified electrostatic interactions between DS and phospholipid. A maximal area reduction of DeltaA = 2.7 A(2) per DMPC molecule is observed. The lipid main-phase transition temperature increases upon formation of DMPC/Ca(2+)/DS-complexes. Lipid area compression after addition of DS and Ca(2+) to the subphase was also observed in monolayer experiments. A decrease in surface tension of up to 3.5 mN/m at constant molecular area was observed. DS binds to the lipid headgroups by formation of Ca(2+) bridges without penetrating the hydrophobic region. We suggest that area compression is the result of an attractive electrostatic interaction between neighboring lipid molecules induced by high local Ca(2+) concentration due to the presence of DS. X-ray diffraction experiments demonstrate that DS binding to apposing bilayers reduces bilayer separation. We speculate that DS binding alters the phase state of low-density lipoproteins that associate with polyelectrolytes of the arterial connective tissue in the early stages of arteriosclerosis.     

A Molecular Dynamics Simulation Study of Nanomechanical Properties of Asymmetric Lipid Bilayer

A very important part of the living cells of biological systems is the lipid membrane. The mechanical properties of this membrane play an important role in biophysical studies. Investigation as to how the insertion of additional phospholipids in one leaflet of a bilayer affects the physical properties of the obtained asymmetric lipid membrane is of recent practical interest. In this work a coarse-grained molecular dynamics simulation was carried out in order to compute the pressure tensor, the lateral pressure, the surface tension and the first moment of lateral pressure in each leaflet of such a bilayer. Our simulations indicate that adding more phospholipids into one monolayer results in asymmetrical changes in the lateral pressure of the individual bilayer leaflets. Interestingly, it has been observed that a change in phospholipid density in one leaflet affects the physical properties of unperturbed leaflet as well. The asymmetric behavior of the physical properties of the two leaflets as a result of a change in the contribution of the various intermolecular forces in the presence of additional phospholipids may be expressed formally.