Dimyristoylphosphatidylserine Research Articles

Effect of Anionic Lipids on Mammalian Plasma Cell Membrane Properties.

The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. Grazing incidence X-ray diffraction and X-ray and neutron reflectivity have been used to characterize lipid packing and solvation, while electrochemical and infrared spectroscopic methods have been employed to probe phase behavior in an applied electric field. Introducing a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into bilayers of zwitterionic dimyristoylphosphatidylethanolamine (DMPE) results in a significant change in the bilayer response to an applied field: the tilt of the hydrocarbon chains increases before returning to the original tilt angle on detachment of the bilayer. Equimolar mixtures, with slightly closer chain packing, exhibit a similar but weaker response. The latter also tend to incorporate more solvent during this electrochemical phase transition, at levels similar to those of pure DMPS. Reflectivity measurements reveal greater solvation of lipid layers for DMPS > 30 mol %, matching the greater propensity for DMPS-rich bilayers to incorporate water. Taken together, the data indicate that the range of 10-35 mol % DMPS provides optimum bilayer properties (in flexibility and function as a barrier), which may explain why the DMPS content of cell membranes tends to be found within this range.

Folding Behaviour and Antibacterial Activity of Ionic Complementary Peptide EAK-16

Aim: A major challenge in the development of new antibiotics is the biocompatibility within biological environment. Ionic complementary peptide (EAK-16) from amyloid protein, have the ability to adopt secondary structure conformation at membrane interfaces. This study aimed to investigate the effect of membrane on EAK-16 peptide folding and their antibacterial applications.
 Methodology: We studied secondary structural conformation of EAK-16 using circular dichroism (CD) spectroscopy in an aqueous environment and at membrane bilayers interfaces. Initially, the antibacterial efficacy was investigated against both Gram-positive and Gram-negative bacteria. Membrane mimicking models were synthesised with dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS) lipid vesicles using calcein leakage assay.
 Results: EAK-16 showed transition in secondary structural conformation. In aqueous environment, it was predominantly β-sheets and at membrane interfaces, it was mainly α-helical. EAK-16 peptide was highly active against bacteria (at minimum concentration applied) and membrane leakage was found to be > 60%. This effect was confirmed with both anionic lipids (DMPS) and neutral lipids (DMPC). The helical transition of EAK-16 could be a major factor to disrupt the membrane and bacterial death
 Conclusion: The secondary structural conformation and calcein leakage data suggest that EAK-16 has potential to kill bacteria by adopting helical tilted conformation and membrane perturbation via lysis. This study revealed structure-function relationship of peptide and lipid bilayers to further investigate the mode of pore formation and mode of action of EAK-16 in membrane perturbation and antibacterial efficacy.

How Well Can You Tailor the Charge of Lipid Vesicles?

Knowledge and control of surface charge or potential is important for tailoring colloidal interactions. In this work, we compare widely used zeta potential (ζ) measurements of charged lipid vesicle surface potential to direct measurements using the surface force apparatus (SFA). Our measurements show good agreement between the two techniques. On varying the fraction of anionic lipids dimyristoylphosphatidylserine (DMPS) or dimyristoylphosphatidylglycerol (DMPG) mixed with zwitterionic dimyristoylphosphatidylcholine (DMPC) from 0 to 100 mol % we observed a near-linear increase in membrane surface charge or potential up to 20-30 mol % charged lipids beyond which charge saturation occurred in physiological (high) salt conditions. Similarly, in low salt concentrations, a linear increase in charge/potential was found but only up to ∼5-10 mol % charged lipids beyond which the surface charge or potential leveled off. While a lower degree of ionization is expected due to the lower dielectric constant (ε ∼ 4) of the lipid acyl chain environment, increasing intramembrane electrostatic repulsion between neighboring charged lipid head groups at higher charge loading contributes to charge suppression. Measured potentials in physiological salt solutions were consistent with predictions using the Gouy-Chapman-Stern-Grahame (GCSG) model of the electrical double layer with Langmuir binding of counterions, but in low salt conditions, the model significantly overestimated the surface charge/potential. The much lower ionization in low salt (maximum ∼1-2% of total lipids ionized) instead was consistent with counterion condensation at the bilayer surface which limited the charge that could be obtained. The strong interplay between membrane composition, lipid headgroup ionization, electrolyte concentration, and solution pH complicates exact prediction and tuning of membrane surface charge for applications. However, the theoretical frameworks used here can provide guidelines to understand this interplay and establish a range of achievable potentials for a system and predict the response to triggers like pH and salt concentration changes.

Effect of bilayer charge on lipoprotein lipid exchange.

Lipoproteins play a key role in the onset and development of atherosclerosis, the formation of lipid plaques at blood vessel walls. The plaque formation, as well as subsequent calcification, involves not only endothelial cells but also connective tissue, and is closely related to a wide range of cardiovascular syndromes, that together constitute the number one cause of death in the Western World. High (HDL) and low (LDL) density lipoproteins are of particular interest in relation to atherosclerosis, due to their protective and harmful effects, respectively. In an effort to elucidate the molecular mechanisms underlying this, and to identify factors determining lipid deposition and exchange at lipid membranes, we here employ neutron reflection (NR) and quartz crystal microbalance with dissipation (QCM-D) to study the effect of membrane charge on lipoprotein deposition and lipid exchange. Dimyristoylphosphatidylcholine (DMPC) bilayers containing varying amounts of negatively charged dimyristoylphosphatidylserine (DMPS) were used to vary membrane charge. It was found that the amount of hydrogenous material deposited from either HDL or LDL to the bilayer depends only weakly on membrane charge density. In contrast, increasing membrane charge resulted in an increase in the amount of lipids removed from the supported lipid bilayer, an effect particularly pronounced for LDL. The latter effects are in line with previously reported observations on atherosclerotic plaque prone regions of long-term hyperlipidaemia and type 2 diabetic patients, and may also provide some molecular clues into the relation between oxidative stress and atherosclerosis.

X-Ray Reflectometry of DMPS Monolayers on a Water Substrate

The molecular structure of dimyristoyl phosphatidylserine (DMPS) monolayers on a water substrate in different phase states has been investigated under normal conditions by X-ray reflectometry with a photon energy of ~ 8 keV. According to the experimental data, the transition from a two-dimensional expanded liquid state to a solid gel state (liquid crystal) accompanied by the ordering of the hydrocarbon tails of the DMPS molecule occurs in the monolayer as the surface pressure rises. The monolayer thickness is (20 +/- 3) Angstrom and (28 +/- 2) Angstrom in the liquid and solid phases, respectively, with the deflection angle of the molecular tail axis from the normal to the surface in the gel phase being (26 +/- 8) deg. At least a twofold decrease in the degree of hydration of the polar lipid groups also occurs under two-dimensional monolayer compression. The reflectometry data have been analyzed using two approaches: under the assumption about the presence of two layers with different electron densities in the monolayer and without any assumptions about the transverse surface structure. Both approaches demonstrate satisfactory agreement between themselves in describing the experimental results.

The electrochemical phase behaviour of chemically asymmetric lipid bilayers supported at Au(111) electrodes

Chemically asymmetric phospholipid bilayers supported on Au(111) surfaces have been studied with differential capacitance and chronocoulometry measurements. The bilayers were prepared using Langmuir-Blodgett deposition, followed by Langmuir-Schaeffer deposition using a different molecule. Combinations of three phospholipids with common hydrocarbon tail groups were compared: dimyristoyl phosphatidyl choline (DMPC), dimyristoyl phosphatidyl ethanolamine (DMPE) and dimyristoyl phosphatidyl serine (DMPS). DMPC and DMPE are zwitterionic and DMPS is anionic in the electrolyte used. The asymmetric bilayers containing DMPS gave distinct electrochemical responses depending on whether the DMPS was deposited first, onto Au, or second, onto another lipid, indicating that asymmetry was maintained over the timescale of the experiment. The results for DMPE and DMPC combinations suggest similar headgroup conformations in the two bilayers. The relationship between the location of the charged molecule and the electrochemical properties is complex but in all cases, DMPS tends to raise bilayer capacitance and DMPE tends to lower capacitance. These observations can be explained by the relatively higher solvation of the charged DMPS molecules and tight packing of DMPE molecules, which leads to exclusion of solvent from the bilayer.

X-ray study of the structure of phospholipid monolayers on the water surface

The possibility of laboratory X-ray reflectometry study of the structure of dimyristoyl phosphatidylserine (DMPS) phospholipid monolayers on the water surface in various phase states has been demonstrated.

Changes in lipid bilayer structure caused by the helix-to-sheet transition of an HIV-1 gp41 fusion peptide derivative

HIV-1, like other enveloped viruses, undergoes fusion with the cell membrane to infect it. Viral coat proteins are thought to bind the virus to the membrane and actively fuse the viral and cellular membranes together. The actual molecular mechanism of fusion is challenging to visualize, resulting in the use of model systems. Here, the bilayer curvature modifying properties of a synthetic variant of the HIV-1 gp41 fusion peptide with lipid bilayer vesicles composed of a mixture of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS) were studied. In 7:3 DMPC:DMPS vesicles made with deuterium-labeled DMPC, the peptide was observed to undergo a concentration-dependent conformational transition between an α-helix and an antiparallel β-sheet. Through the use of small-angle neutron scattering (SANS) and selective deuterium labeling, it was revealed that conformational transition of the peptide is also accompanied by a transition in the structure of the lipid bilayer. In addition to changes in the distribution of the lipid between the leaflets of the vesicle, the SANS data are consistent with two regions having different thicknesses. Of the two different bilayer structures, the one corresponding to the smaller area fraction, being ∼8% of the vesicle area, is much thicker than the remainder of the vesicle, which suggests that there are regions of localized negative curvature similar to what takes place at the point of contact between two membranes immediately preceding fusion.

Biophysical study of the non-steroidal anti-inflammatory drugs (NSAID) ibuprofen, naproxen and diclofenac with phosphatidylserine bilayer membranes

Non-steroidal anti-inflammatory drugs (NSAIDs) represent an effective pain treatment option and therefore one of the most sold therapeutic agents worldwide. The study of the molecular interactions responsible for their physiological activity, but also for their side effects, is therefore important. This report presents data on the interaction of the most consumed NSAIDs (ibuprofen, naproxen and diclofenac) with one main phospholipid in eukaryotic cells, dimyristoylphosphatidylserine (DMPS). The applied techniques are Fourier-transform infrared spectroscopy (FTIR), with which in transmission the gel to liquid crystalline phase transition of the acyl chains in the absence and presence of the NSAID are monitored, supplemented by differential scanning calorimetry (DSC) data on the phase transition. FTIR in reflection (ATR, attenuated total reflectance) is applied to record the dependence of the interactions of the NSAID with particular functional groups observed in the DMPS spectrum such as the ester carbonyl and phosphate vibrational bands. With Förster resonance energy transfer (FRET) a possible intercalation of the NSAID into the DMPS liposomes and with isothermal titration calorimetry (ITC) the thermodynamics of the interaction are monitored. The data show that the NSAID react in a particular way with this lipid, but in some parameters the three NSAID clearly differ, with which now a clear picture of the interaction processes is possible.

Ionic strength dependent vesicle adsorption and phase behavior of anionic phospholipids on a gold substrate.

The authors report on the effect of ionic strength on the formation of supported vesicle layers of anionic phospholipids 1,2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol (DMPG) and dimyristoylphosphatidylserine (DMPS) onto gold. Using quartz crystal microbalance with dissipation monitoring the authors show that vesicle adsorption is mainly governed by NaCl concentration, reflecting the importance of electrostatic interactions in anionic lipids, as compared to zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine. At low ionic strength, low or no adsorption is observed as a result of vesicle-vesicle electrostatic repulsion. At medium ionic strength, the negative charges of DMPG and DMPS are screened resulting in larger adsorption and a highly dissipative intact vesicle layer. In addition, DMPS exhibits a peculiar behavior at high ionic strength that depends on the temperature of the process.

Effect of lipid head groups on double-layered two-dimensional crystals formed by aquaporin-0.

Aquaporin-0 (AQP0) is a lens-specific water channel that also forms membrane junctions. Reconstitution of AQP0 with dimyristoyl phosphatidylcholine (DMPC) and E. coli polar lipids (EPL) yielded well-ordered, double-layered two-dimensional (2D) crystals that allowed electron crystallographic structure determination of the AQP0-mediated membrane junction. The interacting tetramers in the two crystalline layers are exactly in register, resulting in crystals with p422 symmetry. The high-resolution density maps also allowed modeling of the annular lipids surrounding the tetramers. Comparison of the DMPC and EPL bilayers suggested that the lipid head groups do not play an important role in the interaction of annular lipids with AQP0. We now reconstituted AQP0 with the anionic lipid dimyristoyl phosphatidylglycerol (DMPG), which yielded a mixture of 2D crystals with different symmetries. The different crystal symmetries result from shifts between the two crystalline layers, suggesting that the negatively charged PG head group destabilizes the interaction between the extracellular AQP0 surfaces. Reconstitution of AQP0 with dimyristoyl phosphatidylserine (DMPS), another anionic lipid, yielded crystals that had the usual p422 symmetry, but the crystals showed a pH-dependent tendency to stack through their cytoplasmic surfaces. Finally, AQP0 failed to reconstitute into membranes that were composed of more than 40% dimyristoyl phosphatidic acid (DMPA). Hence, although DMPG, DMPS, and DMPA are all negatively charged lipids, they have very different effects on AQP0 2D crystals, illustrating the importance of the specific lipid head group chemistry beyond its mere charge.

A study of HIV-1 FP inhibition by GBV-C peptides using lipid nano-assemblies

Abstract Langmuir–Blodgett films (LBs) and supported lipid bilayers (SLBs) of dimyristoylphosphatidylcholine (DMPC)–dimyristoylphosphatidylserine (DMPS) (3:2) were used to investigate the way that a GBV-C peptide (P45) inhibits the immunodeficiency human virus fusion peptide (HIV-1 FP) action at membrane level. Supported lipid bilayers (SLBs) were prepared by direct adsorption of a liposomal dispersion on solid mica slides and Langmuir–Blodgett films (LBs) by a deposition of a monolayer onto mica solid surface at different compression pressures. The behaviour of P45, HIV-1 FP and a mixture of P45 and HIV-1 FP (1:1) were monitored in the two phospholipid membrane models by fluorescence microscopy (FM) and atomic force microscopy (AFM). Experiments with SLBs confirmed that P45 inhibited HIV-1 FP action in vitro. LBs obtained at 10 and 25 mN m−1 confirmed different lipid interactions for DMPC/DMPS (3:2) in combination with either P45 (8:2), HIV-1 FP (8:2), or P45 and HIV-1 FP (8:1:1). The P45 peptide was confirmed to modulate the action of HIV-1 FP. Furthermore, FM and AFM images showed that HIV-1 FP had a pressure-independent membrane-level behaviour when compared with P45 and the P45 + HIV-1 FP (1:1) mixture. This mixture also had dramatic effects on the appearance of liquid expanded (LE)–liquid condensed (LC) phase coexistence as shown by FM and AFM.

Two possible approaches to quantitative analysis of compression diagrams of lipid monolayers

Experimental curves of lateral pressure and Volta potential previously measured vs. area of dimyristoylphosphatidylserine (DMPS) monolayer (PA diagram) (Ermakov et al., 2010) are analyzed in the framework of the model introduced by Ruckenstein and Li (1996, 1998) for lipid clusters. The same curves are described by some empirical parameters as an alternative mechanistic approach. Both approaches agree with each other and describe the compression diagrams at low and high pressures (high and low areas). Analytical expressions for the asymptotic approximations in the cluster model are suggested. The product of pressure and area (equal to the energy of monolayer compression) as well as Volta potential shown in lateral pressure scale are proposed for experimental data presentation suitable for the quantitative analysis. It is also proposed to represent this function, as well as Volta potential vs. the lateral pressure. Monolayer compressibility module evaluated for the “expanded liquid” area was used to describe the shape of experimental curves. This parameter approximates well the shape of the compression diagrams and Volta potential changes if the interface potential is assumed to be proportional to the mechanical work of the monolayer compression.

Preparation of pH-sensitive anionic liposomes designed for drug delivery system (DDS) application.

We prepared pH-sensitive anionic liposomes composed solely of anionic bilayer membrane components that were designed to promote efficient release of entrapped agents in response to acidic pH. The pH-sensitive anionic liposomes showed high dispersion stability at neutral pH, but the fluidity of the bilayer membrane was enhanced in an acidic environment. These liposomes were rather simple and were composed of dimyristoylphosphatidylcholine (DMPC), an anionic bilayer membrane component, and polyoxyethylene sorbitan monostearate (Tween 80). In particular, the present pH-sensitive anionic liposomes showed higher temporal stability than those of conventional DMPC/DPPC liposomes. We found that pHsensitive properties strongly depended on the molecular structure, pKa value, and amount of an incorporated anionic bilayer membrane component, such as sodium oleate (SO), dimyristoylphosphatidylserine (DMPS), or sodium β-sitosterol sulfate (SS). These results provide an opportunity to manipulate liposomal stability in a pH-dependent manner, which could lead to the formulation of a high performance drug delivery system (DDS).

Effect of Electric Field on Structure and Dynamics of Bilayers Formed From Anionic Phospholipids

The effect of molecular structure on ensemble structure and dynamics of phospholipid bilayers has been investigated. Bilayers of dimyristoyl phosphatidylserine (DMPS) supported on Au(111) surfaces were prepared by Langmuir-Blodgett and Langmuir-Schaeffer deposition and studied with a combination of electrochemical measurements and in situ Polarisation Modulation Infrared Reflection Absorption Spectroscopy (PM-IRRAS). DMPS bilayers have relatively large capacitance when compared with those formed from similar molecules and this is attributed to a high solvent content within the bilayer, resulting from the need for solvation of the negatively charged lipid headgroups. Infrared spectra show that the ensemble of molecules is in a gel state, with extended and ordered hydrocarbon chains, similarly to bilayers of dimyristoyl phosphatidylethanolamine (DMPE) molecules, which are of similar shape. The infrared spectra also show that, in contrast to DMPE, the headgroups of DMPS are very strongly hydrated and have higher mobility. This higher mobility allows the re-orientation of the molecules under the influence of an applied electric field: re-orientation both of headgroups and hydrocarbon tail groups is observed. Thus the shape and charge of the molecules in an ensemble have a strong influence on both their structure and dynamics in the presence of an externally applied electric field.

Effect of salt on the interaction of Hal18 with lipid membranes

One of the major obstacles in the development of new antimicrobial peptides as novel antibiotics is salt sensitivity. Hal18, an α-helical subunit of Halocidin isolated from Halocynthia aurantium, has been previously shown to maintain its antimicrobial activity in high salt conditions. The α-helicity of Hal18 in the presence and absence of salt was demonstrated by circular dichroism spectroscopy, which showed that the peptide was mainly unordered containing β-strands and β-turns. However, in the presence of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS) vesicles, Hal18 folded to form α-helices (circa 42%). Furthermore, the structure was not significantly affected by pH or the presence of metal ions. These data were supported by monolayer results showing Hal18 induced stable surface pressure changes in monolayers composed of DMPC (5mNm(-1)) and DMPS (8.5mNm(-1)), which again were not effected by the presence of metal ions or pH. It is proposed that the hydrophobic groove within its molecular architecture enables the peptide to form stable associations with lipid membranes. The balance of hydrophobicity along the Hal18 long axis would also support oblique orientation of the peptide at the membrane interface. Hence, this model of membrane interaction would enable the peptide to penetrate deep into the membrane. This concept is supported by lysis data. Overall, it would appear that this peptide is a potential candidate for future AMP design for use in high salt environments.

Affinity of Four Polar Neurotransmitters for Lipid Bilayer Membranes

Weak interactions of neurotransmitters and the lipid matrix in the synaptic membrane have been hypothesized to play a role in synaptic transmission of nerve signals, particularly with respect to receptor desensitization (Cantor, R. S. Biochemistry 2003, 42, 11891). The strength of such interactions, however, was not measured, and this is an obvious impediment for further evaluation and understanding of a possible role for desensitization. We have used dialysis equilibrium to directly measure the net affinity of selected neurotransmitters for lipid membranes and analyzed this affinity data with respect to calorimetric measurements and molecular dynamics simulations. We studied an anionic (glutamate), a cationic (acetylcholine), and two zwitterionic (γ-aminobutyric acid and glycine) neurotransmitters, and membranes of pure dimyristoyl phosphatidylcholine (DMPC), DMPC doped with 10% anionic lipid (dimyristoyl phosphatidylglycerol, DMPG, or dimyristoyl phosphatidylserine, DMPS), or 1:1 mixtures of dipalmitoyl phosphatidylcholine (DPPC) and dilauroyl phosphatidylcholine (DLPC). The results showed a remarkable variability among the investigated systems. For example, the chloride salt of acetylcholine interacts unfavorably with DMPC and is thus preferentially excluded from the membrane's hydration layer. Conversely, the zwitterionic neurotransmitters are attracted to membranes with 10% anionic lipid and their local concentration at the interface is 5-10 times larger than in the aqueous bulk. The simulations suggest that this attraction mainly relies on electrostatic interactions of the amino group of the neurotransmitter and the lipid phosphate. We conclude that moderate attraction to lipid membranes occurs for some polar neurotransmitters and hence that one premise for a theory of bilayer-mediated modulation of nerve transmission seems to be fulfilled. However, the strong variability in interaction strengths also shows that this attraction is not an inherent property of all neurotransmitters.

Structure and dynamics of phospholipid bilayer films under electrochemical control

Vesicle fusion was used to deposit mixed dimyristoyl phosphatidylethanolamine–dimyristoyl phosphatidylserine (DMPE–DMPS) phospholipid bilayers on Au electrodes. Bilayer structure and composition, when exposed to aqueous NaF and subject to an applied electrochemical potential, were studied using electrochemical, spectroscopic and neutron reflectivity (NR) techniques. Interfacial capacitance data indicate the formation of compact films. Chronocolometric data show that surface charge is significantly altered by the presence of lipid in the potential range −0.75 < E/V (Ag|AgCl) < 0.35. NR measurements were made on lipid films in which the hydrocarbon tails were either fully hydrogenous (h-DMPE–h-DMPS) or perdeuterated (d-DMPE–d-DMPS), in each case serially exposed to D2O and H2O electrolytes and subject to different applied potentials. Guided by simulations of candidate interfacial structures, these yield the spatial distributions of lipid and solvent within the layers. Adjacent to the electrode, a compact inner leaflet is formed, with potential-dependent solvent volume fraction in the range 0.09 < ϕS < 0.19; there was no evidence of an intervening water layer. The outer leaflet contains rather more solvent, 0.52 < ϕS < 0.55. NR-derived film thickness and PM-IRRAS intensity data show that the lipid molecules are tilted from the surface normal by ca. 26°. Bilayer solvation and charge data show a strong correlation for the inner leaflet and very little for the outer leaflet.

Effect of headgroup on the dipole potential of phospholipid vesicles

The dipole potentials, psi (d), of phospholipid vesicles composed of pure dimyristoylphosphatidylcholine (DMPC) or vesicles in which 50 mol% of the DMPC was substituted by dimyristoylphosphatidylserine (DMPS), dimyristoylphosphatidylglycerol (DMPG), dimyristoylethanolamine (DMPE), dimyristoylphosphatidic acid (DMPA) or monomyristoylphosphatidylcholine (MMPC) were measured via a fluorescent ratiometric method utilizing the probe di-8-ANEPPS. The PS and PG headgroups were found to cause only minor changes in psi (d). PE caused an increase in psi (d) of 51 mV. This could be explained by a decrease in the dielectric constant of the glycerol backbone region as well as a movement of the P(-)-N(+) dipole of the less bulky PE headgroup to a position more parallel to the membrane surface than in PC. The negatively charged PA headgroup increases psi (d) by 215 mV relative to PC alone. This indicates that the positive pole of the dipole predominantly responsible for the dipole potential is located at a position closer to the interior of the membrane than the phosphate group. The increase in the charge of the negative pole of the dipole by the phosphate group of PA increases the electrical potential drop across the lipid headgroup region. The incorporation of the single chain lipid MMPC into the membrane causes a decrease in psi (d) of 142 mV. This can be explained by a decrease in packing density within the membrane of carbonyl dipoles from the sn-2 chain of DMPC. The results presented should contribute to a better understanding of the electrical effect of lipid headgroups on the functioning of membrane proteins.

Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study

Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10 kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.