From glioblastoma to COVID-19 ­ role of oxysterols in the human organism / Od glejaka po COVID-19 - rola oksysteroli w organizmie czlowieka.

Cholesterol is a precursor molecule for vitamin D, bile acids, and steroid hormones. Its oxidized forms, called oxysterols are by-products for synthesis, but also regulate cholesterolâs metabolism through different cell receptors. Cholesterol and oxysterols are important cell membrane components. Oxysterols show more biological activity than cholesterol itself, due to their pleiotropic cell effects. Oxysterol, contrary to cholesterol can cross the blood-brain barier and influence the nervous system. The etiology and pathogenesis of cancer can also be influenced by oxysterols. Elevated levels of oxysterol is often observed in many pathological state: diabetes, atherosclerosis, dementia, or endometriosis. Cholesterolâs oxidized forms can regulate immunity by activation or suppression of the immune cell during virus infection and inflammation.

Cholesterol and Cardiolipin Importance in Local Anesthetics-Membrane Interactions: The Langmuir Monolayer Study.

Local anesthetics (LAs) are known to act on membrane level; however, the molecular mechanism of their activity is still not fully understood. One hypothesis holds that these drugs can incorporate into lipid membrane of nerve cells and in this way change conformation of channel proteins responsible for transport of sodium ions. However, the action of anesthetics is not limited to nerve cells. These drugs also affect other types of cells and organelles, causing severe side effects. In this paper, we applied Langmuir monolayers-as model of cellular membranes-and investigated interactions between selected amide-type local anesthetics (lidocaine prilocaine, mepivacaine and ropivacaine, in the form of hydrochlorides) and lipid components of natural membranes: cholesterol, POPC and cardiolipin (CL) and their mixtures (POPC/cholesterol and POPC/CL/cholesterol), which can serve as simplified models of nerve cell membranes, erythrocytes, and mitochondria. The influence of the drug was monitored by registering the surface pressure (π) as a function of surface area per molecule (A) in a monolayer in the presence of the drug in the subphase. The structure of lipid monolayers on subphases containing and devoid of the studied drugs were visualized with Brewster angle microscopy (BAM). Langmuir monolayer studies complemented with surface visualization technique reveal the expansion and fluidization of lipid monolayers, with the most pronounced effect observed for cardiolipin. In mixed systems, the effect of LAs was found to depend on cholesterol proportion. The observed fluidization of membranes by local anesthetics may negatively affect cells functioning and therefore can explain side effects of these drugs both on the cardiovascular and nervous systems.

The Effect of Dextran Sulfate-as Model Glycosaminoglycan Analogue-on Membrane Lipids: DPPC, Cholesterol, and DPPC-Cholesterol Mixture. The Monolayer Study.

Glycosaminoglycans (GAGs) are essential components of the extracellular matrices (ECMs) located on the outer surface of cellular membranes. They belong to the group of polysaccharides involved in diverse biological processes acting on the surface and across natural lipid membranes. Recently, particular attention has been focused on possible role of GAGs in the amyloid deposits. The amyloid formation is related to a disorder in protein folding, causing that soluble-in normal conditions-peptides become deposited extracellularly as insoluble fibrils, impairing tissue structure and its function. One of the hypothesis holds that GAGs may inhibit amyloid formation by interacting with the lipid membrane by blocking the accumulation of protein aggregates on the membrane surface. Although the biophysical properties of GAGs are described rather well, little is known about the nature of association between these polysaccharides and components of natural cell membranes. Therefore, a study of GAGs influence on membrane lipids is of particular importance. The aim of the present work is to get insight into the effect of hydrophilic dextran sulfate (DS)-that can be considered as GAG analogue-on membrane lipids organization. This study was based on examining interactions between DS sodium salt of molecular weight equal to about 40 kDa (DS40), dissolved in water subphase, and a model membrane, mimicked as Langmuir monolayer, formed by representative natural membrane lipids: cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as well as their mixtures. Due to the fact that calcium ions in excess may accumulate in the lipid membrane, attracting high molecular weight molecules to their surface, the influence of calcium ions present in the subphase on the DS40 activity has also been examined. It has been found that negatively charged DS, forming a sublayer underneath the monolayer, barely interacts with membrane lipids; however, in the presence of calcium ions the electrostatic interactions between DS40 and lipid membrane are significantly enhanced, leading to the formation of network-like crystalline structures at the surface of model membrane, which can prevent incorporation and interaction with other extracellular molecules, e.g., proteins.

Oxysterols Versus Cholesterol in Model Neuronal Membrane. I. The Case of 7-Ketocholesterol. The Langmuir Monolayer Study.

Oxysterols are products of cholesterol oxidation. They can be formed endogenously (in both enzymatic and non-enzymatic reactions) as well as exogenously (delivered with food). Recent studies clearly demonstrate cytotoxic properties of these compounds, being mainly due to their incorporation into natural lipid bilayers. This process can influence mechanical and physicochemical properties of biomembrane-mainly by modifying the interactions between its components, which may result in the disruption of proper functioning of cell membrane and could lead to its degradation. Therefore, it can be assumed that oxysterols may affect the initiation of neurodegenerative diseases, including Alzheimer's disease. However, the mode of action of these molecules at the molecular level is not fully known. To get a better understanding of the role of oxysterols in neurodegeneration, it is of great importance to examine mutual interactions between oxysterols and neuronal membrane components. One of the most promising techniques that can be used to analyze such interactions is the Langmuir monolayer technique. In this work, we have prepared an artificial neuronal membrane modeled as multicomponent Langmuir monolayer built up with cholesterol, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and sphingomyelin (SM). To examine whether there are any changes in the membrane properties under oxidative stress, in this paper we have investigated the impact of the representative ring-oxidized oxysterol: 7-ketocholesterol (7-KC). Our results show that replacing cholesterol with 7-KC increases the interaction between molecules in the model membrane.

The influence of an antitumor lipid - erucylphosphocholine - on artificial lipid raft system modeled as Langmuir monolayer.

Outer layer of cellular membrane contains ordered domains enriched in cholesterol and sphingolipids, called 'lipid rafts', which play various biological roles, i.e., are involved in the induction of cell death by apoptosis. Recent studies have shown that these domains may constitute binding sites for selected drugs. For example alkylphosphocholines (APCs), which are new-generation antitumor agents characterized by high selectivity and broad spectrum of activity, are known to have their molecular targets located at cellular membrane and their selective accumulation in tumor cells has been hypothesized to be linked with the alternation of biophysical properties of lipid rafts. To get a deeper insight into this issue, interactions between representative APC: erucylphosphocholine, and artificial lipid raft system, modeled as Langmuir monolayer (composed of cholesterol and sphingomyelin mixed in 1:2 proportion) were investigated. The Langmuir monolayer experiments, based on recording surface pressure-area isotherms, were complemented with Brewster angle microscopy results, which enabled direct visualization of the monolayers structure. In addition, the investigated monolayers were transferred onto solid supports and studied with AFM. The interactions between model raft system and erucylphosphocholine were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with ΔG(exc) function). The obtained results indicate that erucylphosphocholine introduced to raft-mimicking model membrane causes fluidizing effect and weakens the interactions between cholesterol and sphingomyelin, which results in phase separation at high surface pressures. This leads to the redistribution of cholesterol molecules in model raft, which confirms the results observed in biological studies.

Cyclosporin A in Membrane Lipids Environment: Implications for Antimalarial Activity of the Drug--The Langmuir Monolayer Studies.

Cyclosporin A (CsA), a hydrophobic cyclic peptide produced by the fungus Tolypocladium inflatum, is well known for its high efficiency as an immunosuppressor for transplanted organs and anti-inflammatory properties; however, it is also active as antiparasitic (antimalarial) drug. Antimalarial mechanism of CsA action lacks a detailed understanding at molecular level. Due to a high lipophilicity of CsA, it is able to interact with lipids of cellular membrane; however, molecular targets of this drug are still unknown. To get a deeper insight into the mode of antimalarial activity of CsA, it is of utmost importance to examine its interactions with membrane components. To reach this goal, the Langmuir monolayer technique, which serves as a very useful, easy to handle and controllable model of biomembranes, has been employed. In this work, the interactions between CsA and main membrane lipids, i.e., cholesterol (Chol), 2-oleoyl-1-palmitoyl-3-phosphocholine (POPC), and sphingomyelin (SM), have been investigated. Attractive interactions are observed only for CsA mixtures with SM, while repulsive forces occur in systems containing remaining membrane lipids. Taking into consideration mutual interactions between membrane lipids (Chol-SM; Chol-POPC and SM-POPC), the behavior of CsA in model erythrocyte membrane of normal and infected cells has been analyzed. Our results prove strong affinity of CsA to SM in membrane environment. Since normal and parasitized erythrocytes differ significantly in the level of SM, this phospholipid may be considered as a molecular target for antimalarial activity of CsA.

Cholesterol as a factor regulating the influence of natural (PAF and lysoPAF) vs synthetic (ED) ether lipids on model lipid membranes.

In this work we have performed a comparative study on the effect of antineoplastic ether lipid-edelfosine (ED), its natural analogs - Platelet Activating Factor (PAF) and its precursor (lyso-PAF), both lacking anticancer properties, on cholesterol/phosphatidylcholine (Chol/PC) monolayers, serving as model membranes. Since all the above ether lipids are membrane active, it can be expected that their effect on membranes may differentiate their biological activity. Our investigations were aimed at studying potential relationship of the effect of ED, PAF and lyso-PAF on model membranes, differing in condensation. We have modified molecular packing of Chol/PC model systems either by increasing the level of sterol in the system or changing the structure of PC, while keeping the same sterol content. Additionally, we have performed a detailed comparison of the miscibility of ED, PAF and lyso-PAF with various membrane lipids. The collected data evidenced that all the investigated ether lipids influence Chol/PC films in the same way; however, in a different magnitude. Moreover, the interactions of ED, PAF and lyso-PAF with model membranes were the strongest at the highest level of sterol in the system. A thorough analysis of the obtained results has proved that the effect of the investigated ether lipids on membranes is not dependent on the condensation of the system, but it is strongly determined by the concentration of cholesterol. Since ED was found to interact with model membranes stronger than PAF and lyso-PAF, we have suggested that this fact may contribute to differences in cytotoxicity of these compounds.

Affinity of alkylphosphocholines to biological membrane of prostate cancer: studies in natural and model systems.

The effectiveness of two alkylphosphocholines (APCs), hexadecylphosphocholine (miltefosine) and erucylphosphocholine to combat prostate cancer has been studied in vitro with artificial cancerous membrane, modelled with the Langmuir monolayer technique, and on cell line (Du-145). Studies performed with the Langmuir method indicate that both the investigated drugs have the affinity to the monolayer mimicking prostate cancer membrane (composed of cholesterol:POPC = 0.428) and the drug-membrane interactions are stronger for erucylphosphocholine as compared to hexadecylphosphocholine. Moreover, both studied drugs were found to fluidize the model membrane, which may lead to apoptosis. Indeed, biological studies confirmed that in Du-145 cell line both investigated alkylphosphocholines cause cell death primarily by apoptosis while necrotic cells constitute only a small percentage of APC-treated cells.

Advantages of the classical thermodynamic analysis of single-and multi-component Langmuir monolayers from molecules of biomedical importance-theory and applications.

The Langmuir monolayer technique has been successfully used for decades to model biological membranes and processes occurring at their interfaces. Classically, this method involves surface pressure measurements to study interactions within membrane components as well as between external bioactive molecules (e.g. drugs) and the membrane. In recent years, surface-sensitive techniques were developed to investigate monolayers in situ; however, the obtained results are in many cases insufficient for a full characterization of biomolecule-membrane interactions. As result, description of systems using parameters such as mixing or excess thermodynamic functions is still relevant, valuable and irreplaceable in biophysical research. This review article summarizes the theory of thermodynamics of single- and multi-component Langmuir monolayers. In addition, recent applications of this approach to characterize surface behaviour and interactions (e.g. orientation of bipolar molecules, drug-membrane affinity, lateral membrane heterogeneity) are presented.

Oxysterols in Cell Viability, Phospholipidosis and Extracellular Vesicles Production in a Lung Cancer Model.

The study carried out systematic research on the influence of selected oxysterols on cells viability, phospholipidosis and the level of secreted extracellular vesicles. Three oxidized cholesterol derivatives, namely 7α-hydroxycholesterol (7α-OH), 7- ketocholesterol (7-K) and 24(S)-hydroxycholesterol (24(S)-OH) were tested in three different concentrations: 50 µM, 100 µM and 200 µM for 24 h incubation with A549 lung cancer cell line. All the studied oxysterols were found to alter cells viability. The lowest survival rate of the cells was observed after 24 h of 7-K treatment, slightly better for 7α-OH while cells incubated with 24(S)-OH had the best survival rate among the oxysterols used. 7-K increased phospholipids accumulation in cells, however, most noticeable effect was noticed for 24(S)-OH. Changes in the level of extracellular vesicles secreted in cells culture after the treatment with oxysterols were also observed. It was found that all oxysterols used increased the level of secreted vesicles, both exosomes and ectosomes. The strongest effect was noticed for 24(S)-OH. Taken together, these results suggest that 7-K is the most potent inducer of cancer cell death, while 7α-OH is slightly less potent in this respect. The lower cytotoxic effect of 24(S)-OH correlates with greater phospholipids accumulation, extracellular vesicles production and better cells survival.

Insight into the Molecular Mechanism of Surface Interactions of Phosphatidylcholines─Langmuir Monolayer Study Complemented with Molecular Dynamics Simulations.

Mutual interactions between components of biological membranes are pivotal for maintaining their proper biophysical properties, such as stability, fluidity, or permeability. The main building blocks of biomembranes are lipids, among which the most important are phospholipids (mainly phosphatidylcholines (PCs)) and sterols (mainly cholesterol). Although there is a plethora of reports on interactions between PCs, as well as between PCs and cholesterol, their molecular mechanism has not yet been fully explained. Therefore, to resolve this issue, we carried out systematic investigations based on the classical Langmuir monolayer technique complemented with molecular dynamics simulations. The studies involved systems containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) analogues possessing in the structure one or two polar functional groups similar to those of DPPC. The interactions and rheological properties of binary mixtures of DPPC analogues with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol were compared with reference systems (DPPC/POPC and DPPC/cholesterol). This pointed to the importance of the ternary amine group in PC/cholesterol interactions, while in PC mixtures, the phosphate group played a key role. In both cases, the esterified glycerol group had an effect on the magnitude of interactions. The obtained results are crucial for establishing structure-property relationships as well as for designing substitutes for natural lipids.

Lithocholic acid-based oligomers as drug delivery candidates targeting model of lipid raft.

This study presents a new approach to designing a lithocholic acid functionalized oligomer (OLithocholicAA-X) that can be used as a drug carrier with additional, beneficial activity. Namely, this novel oligomer can incorporate an anti-cancer drug due to the application of an effective backbone as its component (lithocholic acid) alone is known to have anticancer activity. The oligomer was synthesized and characterized in detail by nuclear magnetic resonance, attenuated total reflectance Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, thermal analysis, and mass spectrometry analysis. We selected lipid rafts as potential drug carrier-membrane binding sites. In this respect, we investigated the effects of OLithocholicAA-X on model lipid raft of normal and altered composition, containing an increased amount of cholesterol (Chol) or sphingomyelin (SM), using Langmuir monolayers and liposomes. The surface topography of the studied monolayers was additionally investigated by atomic force microscopy (AFM). The obtained results showed that the investigated oligomer has affinity for a system that mimics a normal lipid raft (SM:Chol 2:1). On the other hand, for systems with an excess of SM or Chol, thermodynamically unfavorable fluidization of the films occurs. Moreover, AFM topographies showed that the amount of SM determines the bioavailability of the oligomer, causing fragmentation of its lattice.

Externalization of phosphatidylserine from inner to outer layer may alter the effect of plant sterols on human erythrocyte membrane - the Langmuir monolayer studies.

One of the factors, which can strongly modify the cell membrane composition, is disordering in membrane asymmetry, resulting from redistribution of lipids from inner to outer layer. Such a disturbance may affect the behavior of various biologically active compounds incorporating into membranes. In this contribution, the relationship between the amounts of phosphatidylserine (PS) in the model outer layer of human erythrocyte (RBC) membrane and the effect induced by a plant sterol (ß-sitosterol) was verified. The experiments were performed on multicomponent Langmuir films imitating red blood cell (RBC) membrane, differing in the contents of PS (0%; 5% and 10%) into which the plant sterol was incorporated in various concentrations. The analysis of experimental results (surface pressure-area isotherms complemented with Brewster Angle Microscopy (BAM) proved that the presence of phosphatidylserine molecules, depending on their contents in the mixed monolayer mimicking RBC membrane, changes its properties and exerts influence on the effect of plant sterol on the model system. The addition of phytosterol into the monolayer that lacks or contains only 5% of PS was found to be of rather weak effect on the properties of the system. However, in the case of the model membrane containing the increased amount (10%) of PS, the incorporation of plant sterol strongly affects the interactions between molecules and caused thermodynamic destabilization of the monolayer imitating RBC membrane. These results allow one to suggest that externalization of phosphatidyserine to the outer membrane leaflet may differentiate the effect of plant sterols on cell membranes of various origins.

Interactions of alkylphosphocholines with model membranes-the Langmuir monolayer study.

Alkylphosphocholines (APCs) belong to a class of synthetic antitumor lipids, which are new-generation anticancer agents. In contrast to traditional antitumor drugs, they do not attack the cell nucleus but, rather, the cellular membrane; however, their mechanism of action is not fully understood. This work compared the interactions of selected APCs [namely, hexadecylphosphocholine (miltefosine), octadecylphosphocholine and erucylphosphocholine] with the most important membrane lipids [cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)] and examined their influence on a model membrane of tumor and normal cells. As a simple model of membranes, Langmuir monolayers prepared by mixing cholesterol either with a saturated phosphatidylcholine (DPPC), for a normal cell membrane, or with an unsaturated one (POPC), for a tumor cell membrane, have been applied. The APC-lipid interactions, based on experimental surface pressure (π) versus mean molecular area (A) isotherms, were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with the ΔG(exc) function). Strong attractive interactions were observed for mixtures of APCs with cholesterol, contrary to the investigated phosphatidylcholines, for which the interactions were found to be weak with a tendency to separation of film components. In ternary monolayers it has been found that the investigated model systems (cholesterol/DPPC/APC vs cholesterol/POPC/APC) differ significantly as regards the interactions between film-forming molecules. The results demonstrate stronger interactions between the components of cholesterol/POPC/APC monolayers compared to cholesterol/POPC film, mimicking tumor cell membranes. In contrast, the interactions in cholesterol/DPPC/APC films were found to be weaker than those in the cholesterol/DPPC system, serving as a model of healthy cell membranes, thus proving that the incorporation of APCs is, from a thermodynamic point of view, unfavorable for binary cholesterol/DPPC monolayers. It can be concluded that the composition of healthy cell membranes is a natural barrier preventing the incorporation of APCs into normal cells.

Site of the Hydroxyl Group Determines the Surface Behavior of Bipolar Chain-Oxidized Cholesterol Derivatives─Langmuir Monolayer Studies Supplemented with Theoretical Calculations.

Cholesterol oxidation products (called oxysterols) are involved in many biological processes, showing both negative (e.g., neurodegenerative) and positive (e.g., antiviral and antimicrobial) effects. The physiological activity of oxysterols is undoubtedly closely related to their structure (i.e., the type and location of the additional polar group in the cholesterol skeleton). In this paper, we focus on determining how a seemingly minor structural change (introduction of a hydroxyl moiety at C(24), C(25), or C(27) in the isooctyl chain of cholesterol) affects the organization of the resulting molecules at the phase boundary. In our research, we supplemented the classic Langmuir monolayer technique, based on the surface pressure and electric surface potential isotherms, with microscopic (BAM) and spectroscopic (PM-IRRAS) techniques, as well as theoretical calculations (DFT and MD). This allowed us to show that 24-OH behaves more like cholesterol and forms stable, rigid monolayers. On the other hand, 27-OH, similar to 25-OH, undergoes the phase transition from monolayer to bilayer structures. Theoretical calculations enabled us to conclude that the formation of bilayers from 27-OH or 25-OH is possible due to the hydrogen bonding between adjacent oxysterol molecules. This observation may help to understand the factors responsible for the unique biological activity (including antiviral and antimicrobial) of 27-OH and 25-OH compared to other oxysterols.

Predicting the packing parameter for lipids in monolayers with the use of molecular dynamics.

Lipid molecules form the backbone of biological membranes. Due to their amphiphilic structure, they can self-organize in a plethora of different structures when in contact with water. The type of self-assembled structure and its curvature depend on so-called shape factor or critical packing parameter, CPP, that can be derived knowing the molecular volume of a lipid (V), optimal surface area (a0) and critical chain length (lc) (see Intermolecular and Surface Forces by Jacob N. Israelachvili, Third Edition, 2011). The value of CPP allows not only to predict the type of self-assembled structure but also is a key factor for molecular interactions, which play a great role both in physiological and pathological conditions. The greatest difficulties arise when calculating the a0 parameter, and although for some typical membrane lipids these values have been determined, there are a number of derivatives for which this parameter, and thus CPP, are unknown. The value of CPP allows not only to predict the type of self-assembled structure but also is a key factor for molecular interactions, which play a great role both in physiological and pathological conditions. So far, the determination of the packing parameter required the use of theoretical models with assumptions deviating from the physical conditions. Here we report a method based on molecular dynamics, which was applied to simulate lipid membranes consisting of cholesterol, oxysterols, sphingolipids, phosphatidylcholines, and phosphatidylethanolamines. For lipid molecules for which CPPs have already been determined, high compliance has been demonstrated. This proves that the method presented herein can be successfully used to determine packing parameters for other membrane lipids and amphiphilic molecules.

Oxysterols can act antiviral through modification of lipid membrane properties - The Langmuir monolayer study.

In this paper we tested how oxysterols influence on fusion process between viral lipid envelope and host cells membranes. For this purpose, the Zika virus was selected, while dendritic cell (DC) and neural cell (NC) membranes were chosen as target membranes. The investigated systems were modeled as multicomponent Langmuir monolayers and characterized using surface manometry and imaging in micro- (Brewster angle microscopy, BAM) and nanoscale (Atomic Force Microscopy, AFM) to monitor local heterogeneity. The fusion process was conducted by mixing viral and host cell membranes devoid and in the presence of oxysterols: 25-hydroxycholesterol (25-OH) and 7ß-hydroxycholesterol (7ß-OH) as representatives of chain- and ring-oxidized oxysterols, respectively. Our results show that oxysterols hinder the fusion with host cell membranes by modifying their biophysical properties. Moreover, oxysterols applied to an already infected membrane reverse the changes caused by the infection. It could therefore be concluded that oxysterols may display antiviral activity in two ways: they prevent the healthy membrane from viral infection by blocking the fusion process; and protect already infected membrane from pathological changes induced by the virus.

Different effects of oxysterols on a model lipid raft - Langmuir monolayer study complemented with theoretical calculations.

Three oxysterols (7ß-hydroxycholesterol; 7ß-OH, 7-ketocholesterol; 7-K and 25-hydroxycholesterol, 25-OH) differing in the site of oxidation (ring system versus chain) and kind of polar group (hydroxyl versus carbonyl) were studied in lipid raft environment using the Langmuir monolayer technique complemented with theoretical calculations. Experiments were performed for the unmodified raft system, composed of sphingomyelin (SM) and cholesterol (Chol), and in the next step the raft was modified by the incorporation of oxysterol in different proportions. In the examined three-component system (Chol:SM:oxysterol), apart from interactions between the lipid raft components, the affinity of Chol to its oxidized derivatives also plays an important role. 25-OH was found to enhance interactions between SM and Chol and thus stabilize the raft, contrary to 7ß-OH and 7-K, which exerted the fluidizing effect as well as the destabilization of the raft. Different action of oxysterols on model raft was observed. 7ß-OH and 7-K, which are highly potent inducers of cell death caused raft destabilization, while 25-OH, which is the least toxic of the investigated oxysterols, was found to stabilize the raft.

Comprehensive Approach to the Interpretation of the Electrical Properties of Film-Forming Molecules.

This paper presents a general protocol for the interpretation of the electric surface potential of Langmuir monolayers based on a three-layer capacitor model. The measured values were correlated with the results from DFT molecular dynamics simulations, and, as a result, the local dielectric permittivities and dipole-moment components of molecules organized in the monolayer were obtained. The main advantage of the developed approach is applicability to amphiphiles of any type; irrespective of the structure of the polar head as well as the molecular organization and inclination in the surface film. The developed methodology was successively applied to an atypical surface-active compound, perfluorodecyldecane, and its derivatives containing the hydroxyl, thiol, and carboxyl moiety. The following contributions to the apparent dipole moments connected with the reorientation of water molecules and local dielectric permittivities in the vicinity of polar and apolar molecule parts, respectively, were determined: µw/εw = -0.85 D, εp = 5.00, and εa = 1.80. Moreover, the investigated perfluorodecyldecane derivatives were comprehensively characterized in terms of their surface activity, film rheology, and effective surface dissociation equilibria. The proposed methodology may be crucial for the process of the design and the preliminary characterization of molecules for sensor and material science applications.

Electrical Properties of Membrane Phospholipids in Langmuir Monolayers.

Experimental surface pressure (π) and electric surface potential (ΔV) isotherms were measured for membrane lipids, including the following phosphatidylcholines (PCs)-1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); 1,2-diarachidoyl-sn-glycero-3-phosphocholine (DAPC); and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). In addition, other phospholipids, such as phosphatidylethanolamines (represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE)) and sphingolipids (represented by N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine (SM)) were also studied. The experimental apparent dipole moments (µAexp) of the abovementioned lipids were determined using the Helmholtz equation. The particular contributions to the apparent dipole moments of the investigated molecules connected with their polar (µ⟂p) and apolar parts (µ⟂a) were theoretically calculated for geometrically optimized systems. Using a three-layer capacitor model, introducing the group's apparent dipole moments (calculated herein) and adopting values from other papers to account for the reorientation of water molecules (µ⟂w/εw), as well as the for the local dielectric permittivity in the vicinity of the polar (εp) and apolar (εa) groups, the apparent dipole moments of the investigated molecules were calculated (µAcalc). Since the comparison of the two values (experimental and calculated) resulted in large discrepancies, we developed a new methodology that correlates the results from density functional theory (DFT) molecular modeling with experimentally determined values using multiple linear regression. From the fitted model, the following contributions to the apparent dipole moments were determined: µ⟂w/εw=-1.8±1.4 D; εp=10.2±7.0 and εa=0.95±0.52). Local dielectric permittivity in the vicinity of apolar groups (εa) is much lower compared to that in the vicinity of polar moieties (εp), which is in line with the tendency observed by other authors studying simple molecules with small polar groups. A much higher value for the contributions from the reorientation of water molecules (µ⟂w/εw) has been interpreted as resulting from bulky and strongly hydrated polar groups of phospholipids.