Interactions Between non-ionic Surfactant Vesicles and human stratum corneum in vitro.

Abstract

The effects of non-ionic surfactant vesicles (NSVs) on human skin in vitro were studied in relation to the physico-chemical properties of the vesicles. The interactions between NSVs and skin were visualized using both freeze fracture electron microscopy and confocal laser scanning microscopy. The physico-chemical properties of the NSVs were varied in a systematic way, using a broad series of polyoxyethylene monoalkyl ether type surfactants (C_nEO_m). The number of oxyethylene units (m) was varied between 3, 7 and 10, and the number of carbon atoms (n) was either 12 or 18. Both the effects of liquid state vesicles composed of ^C12^Eo3,7 ^and C9=9^EO10 surfactants and gel state vesicles (C18EO37) were investigated. After the application of the NS V suspension on the stratum corneum surface two essentially different types of vesicle-skin interactions were visualized. Firstly, an interfacial interaction, involving the adsorption of vesicles, and the deposition of bilayer sheets on the outermost layers of the stratum corneum observed for all NSV formulations tested in this study. Secondly, effects on the ultrastructure of the stratum corneum were observed: the appearance of water pools observed for the liquid state vesicles only, and ultrastructural changes of the intercellular lipid domains are induced only observed after treatment with C₁₂EO₃ NSVs. Neither changes in the ultrastructure of the viable epidermis, nor changes in deeper skin layers were observed.     

The effects of cholesterol and β-sitosterol on the structure of saturated diacylphosphatidylcholine bilayers

The structures of DMPC and DPPC bilayers in unilamellar liposomes, in the presence of 33.3 mol% cholesterol or the plant sterol β-sitosterol, have been studied by small-angle neutron scattering. The bilayer thickness d _L increases in a similar way for both sterols. The repeat distance in multilamellar liposomes, as determined by small-angle X-ray diffraction, is larger in the presence of β-sitosterol than in the presence of cholesterol. We observe that each sterol modifies the interlamellar water layer differently, cholesterol reducing its thickness more efficiently than β-sitosterol, and conclude that cholesterol suppresses bilayer undulations more effectively than β-sitosterol.     

Interaction of enantiomeric alkylacyl and diacylglycerophosphocholines with cholesterol in bilayer membranes

The sn-1 and sn-3 isomers of dioleoylglycerophosphocholine form vesicles of the same size as the racemic lipid. Identical permeability coefficients were found for the diffusion of glucose and chloride across bilayer membranes of vesicles consisting of these lipids. Vesicles made of mixtures of enantiomeric or racemic dioleoyllecithin with 30 mol% cholesterol have identical radii. Cholesterol reduces the permeability of bilayers for glucose and chloride irrespective of the steric configuration of the constituent phospholipid. Increasing concentrations of cholesterol (17, 33 and 50 mol%, respectively) broaden the (CH₂)_n signal in the ¹H-NMR-spectra (90 MHz) of unilamellar vesicles containing sn-1, sn-3 or rac alkyloleoylglycerophosphocholine to the same extent. These results indicate that the steric configuration of phospholipids has no gross effect on the arrangement of phospholipids and cholesterol in bilayer membranes.     

Probing the steric barrier of nonionic surfactant vesicles with melittin

The role of the surface polymer brush of nonionic surfactant vesicles (NSV) in inhibiting interactions with small membrane-perturbing molecules was investigated using the bee venom peptide melittin as a probe. The interaction between melittin and NSV was compared with that of distearoylphosphatidylcholine (DSPC) vesicles and sterically stabilised liposomes (SSL) containing 5 mol% pegylated distearoylphosphatidylethanolamine (DSPE.E₄₄). The degree of melittin interaction with the various vesicles was determined by measuring peptide binding and folding, using intrinsic tryptophan fluorescence and circular dichroism respectively, in addition to monitoring the release of encapsulated carboxyfluorescein dye. NSV composed of 1,2-di-O-octadecyl-rac-glyceryl-3-(ω-dodecaethylene glycol) (2C₁₈E₁₂) showed a strong affinity for melittin, whilst exhibiting ~ 50% less bound peptide than SSL. 2C₁₈E₁₂:Chol vesicles showed reduced melittin interaction, in a manner consistent with Chol incorporation into DSPC vesicles. These results are discussed with respect to the effect of Chol on the in-plane order of 2C₁₈E₁₂ bilayers and consequent attenuation of hydrophobic interactions with the peptide. NSV formed from equimolar mixtures of polyoxyethylene-n-stearoyl ethers C₁₈E₂ and C₁₈E₂₀ showed a greater interaction with melittin than 2C₁₈E₁₂. However, replacing C₁₈E₂₀ with C₁₈E₁₀ was sufficient to achieve an attenuation of melittin interaction similar to that observed in 2C₁₈E₁₂:Chol vesicles. This indicates that the presence of surface polymer brush alone may confer resistance to melittin, provided hydrophobic interactions between the peptide and the vesicles can be minimised, through improved in-plane bilayer order.     

Hydrophobic thickness, lipid surface area and polar region hydration in monounsaturated diacylphosphatidylcholine bilayers: SANS study of effects of cholesterol and β-sitosterol in unilamellar vesicles

The influence of a mammalian sterol cholesterol and a plant sterol β-sitosterol on the structural parameters and hydration of bilayers in unilamellar vesicles made of monounsaturated diacylphosphatidylcholines (diCn:1PC, n = 14-22 is the even number of acyl chain carbons) was studied at 30 °C using small-angle neutron scattering (SANS). Recently published advanced model of lipid bilayer as a three-strip structure was used with a triangular shape of polar head group probability distribution (Ku?erka et al., Models to analyze small-angle neutron scattering from unilamellar lipid vesicles, Physical Review E 69 (2004) Art. No. 051903). It was found that 33 mol% of both sterols increased the thickness of diCn:1PC bilayers with n = 18-22 similarly. β-sitosterol increased the thickness of diC14:1PC and diC16:1PC bilayers a little more than cholesterol. Both sterols increased the surface area per unit cell by cca 12 Å² and the number of water molecules located in the head group region by cca 4 molecules, irrespective to the acyl chain length of diCn:1PC. The structural difference in the side chain between cholesterol and β-sitosterol plays a negligible role in influencing the structural parameters of bilayers studied.     

CRAC motif peptide of the HIV-1 gp41 protein thins SOPC membranes and interacts with cholesterol

This study uses low-angle (LAXS) and wide-angle (WAXS) X-ray synchrotron scattering, volume measurements and thin layer chromatography to determine the structure and interactions of SOPC, SOPC/cholesterol mixtures, SOPC/peptide and SOPC/cholesterol/peptide mixtures. N-acetyl-LWYIK-amide (LWYIK) represents the naturally-occurring CRAC motif segment in the pretransmembrane region of the gp41 protein of HIV-1, and N-acetyl-IWYIK-amide (IWYIK), an unnatural isomer, is used as a control. Both peptides thin the SOPC bilayer by ∼ 3 Å, and cause the area/unit cell (peptide + SOPC) to increase by ∼ 9 Å² from the area/lipid of SOPC at 30 °C (67.0 ± 0.9 Å²). Model fitting suggests that LWYIK's average position is slightly closer to the bilayer center than IWYIK's, and both peptides are just inside of the phosphate headgroup. Both peptides increase the wide-angle spacing d of SOPC without cholesterol, whereas with 50% cholesterol LWYIK increases d but IWYIK decreases d. TLC shows that LWYIK is more hydrophobic than IWYIK; this difference persists in peptide/SOPC 1:9 mole ratio mixtures. Both peptides counteract the chain ordering effect of cholesterol to roughly the same degree, and both decrease K_C, the bending modulus, thus increasing the SOPC membrane fluidity. Both peptides nucleate crystals of cholesterol, but the LWYIK-induced crystals are weaker and dissolve more easily.     

Bilayer polarity and its thermal dependency in the ?o and ?d phases of binary phosphatidylcholine/cholesterol mixtures

Diverse variations in membrane properties are observed in binary phosphatidylcholine/cholesterol mixtures. These mixtures are nonideal, displaying single or phase coexistence, depending on chemical composition and other thermodynamic parameters. When compared with pure phospholipid bilayers, there are changes in water permeability, bilayer thickness and thermomechanical properties, molecular packing and conformational freedom of phospholipid acyl chains, in internal dipolar potential and in lipid lateral diffusion. Based on the phase diagrams for DMPC/cholesterol and DPPC/cholesterol, we compare the equivalent polarity of pure bilayers with specific compositions of these mixtures, by using the Py empirical scale of polarity. Besides the contrast between pure and mixed lipid bilayers, we find that liquid-ordered (?_o) and liquid-disordered (?_d) phases display significantly different polarities. Moreover, in the ?_o phase, the polarities of bilayers and their thermal dependences vary with the chemical composition, showing noteworthy differences for cholesterol proportions at 35, 40, and 45 mol%. At 20 °C, for DMPC/cholesterol at 35 and 45 mol%, the equivalent dielectric constants are 21.8 and 23.8, respectively. Additionally, we illustrate potential implications of polarity in various membrane-based processes and reactions, proposing that for cholesterol containing bilayers, it may also go along with the occurrence of lateral heterogeneity in biological membranes.     

Effects of cholesterol on acyl chain dynamics in multilamellar vesicles of various phosphatidylcholines

Phase modulation fluorescence spectroscopy was used to investigate the influence of cholesterol (0 to 50 mol%) on acyl chain dynamics in multilamellar vesicles of phosphatidylcholine. Four different phosphatidylcholines (DPPC, DOPC, POPC, and egg PC) and six different fluorescent probes (diphenylhexatriene and five anthroyloxy fatty acids) were employed. We found that: (1) Increased cholesterol content had only slight effects on fluorescence lifetimes of the six probes. (2) Increased cholesterol content increased the steady-state fluorescence anisotropy (r) of all the probes except 16-anthroyloxy palmitate (16-AP) in each of the four phosphatidylcholines. (3) Added cholesterol tended to limit the extent of probe rotation (as reflected by r_∞, the infinite-time anisotropy) to a much greater extent than it altered the rate of probe rotation. (4) The tendency for cholesterol to order the structure of the bilayer was greatest in the proximal half of the acyl chains and diminished toward the center of the bilayer. (5) In some phosphatidylcholines the rotation rates of probes located near the bilayer center (diphenylhexatriene and 16-AP) were apparently increased by increasing levels of cholesterol. (6) In several respects dipalmitoylphosphatidylcholine (DPPC) vesicles responded differently to increased cholesterol than vesicles of the other three phosphatidylcholines. (7) A single second-order equation described the relationship between r_∞and r for the five anthroyloxy fatty acid probes in the four different phosphatidylcholines over a wide range of cholesterol content. The data for diphenylhexatriene in the different phosphatidylcholines could not be fit by a single equation.     

Investigating the impact of cholesterol on magnetically aligned sphingomyelin/cholesterol multilamellar vesicles using static 31P NMR

The effect of cholesterol (5–40 mol%) on the magnetic induced orientation of sphingomyelin/cholesterol multilamellar vesicles (MLVs) was examined using static solid state ³¹P NMR spectroscopy. The orientation was modeled assuming an ellipsoidal deformation of the vesicles and was monitored as a function of cholesterol concentration and temperature. In addition, the static ³¹P chemical shift anisotropy (CSA) was used to assess the motional and dynamical changes occurring in the bilayer are reported. An exploration of the factors determining the magnetic orientation in sphingomyelin/cholesterol bilayers from the gel (s_o) to liquid crystalline (or liquid-ordered, l_o) phases is presented and discussed.     

Molecular Dynamics Simulations of PIP2 and PIP3 in Lipid Bilayers: Determination of Ring Orientation, and the Effects of Surface Roughness on a Poisson-Boltzmann Description

Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP₂) and phosphatidylinositol (3,4,5)-trisphosphate (PIP₃) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted ∼40° with respect to the bilayer surface, as compared with 17° for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP₂ and PIP₃ are within an Ångström of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 Å, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of ∼26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the −25 mV surfaces (17.1 ± 0.1 Å for PIP₂ and 19.4 ± 0.3 Å for PIP₃) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 Å estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP₂ and PIP₃ as long as the orientations are judiciously chosen.     

The use of solvent relaxation technique to investigate headgroup hydration and protein binding of simple and mixed phosphatidylcholine/surfactant bilayer membranes

The subject of this report was to investigate headgroup hydration and mobility of two types of mixed lipid vesicles, containing nonionic surfactants; straight chain Brij 98, and polysorbat Tween 80, with the same number of oxyethylene units as Brij, but attached via a sorbitan ring to oleic acid. We used the fluorescence solvent relaxation (SR) approach for the purpose and revealed differences between the two systems. Fluorescent solvent relaxation probes (Prodan, Laurdan, Patman) were found to be localized in mixed lipid vesicles similarly as in pure phospholipid bilayers. The SR parameters (i.e. dynamic Stokes shift, Δν, and the time course of the correlation function, C(t)) of such labels are in the same range in both kinds of systems. Each type of the tested surfactants has its own impact on water organization in the bilayer headgroup region probed by Patman. Brij 98 does not modify the solvation characteristics of the dye. In contrast, Tween 80 apparently dehydrates the headgroup and decreases its mobility. The SR data measured in lipid bilayers in presence of Interferon alfa-2b reveal that this protein, a candidate for non-invasive delivery, affects the bilayer in a different way than the peptide melittin. Interferon alfa-2b binds to mixed lipid bilayers peripherally, whereas melittin is deeply inserted into lipid membranes and affects their headgroup hydration and mobility measurably.     

Perturbation of phospholipid bilayers by DDT

The localization of the effects of DDT (5–50 mol%) addition on the acyl chain dynamics in unilamellar vesicles of two phosphatidylcholines (DPPC and egg PC) has been investigated by steady-state fluorescence polarization of a series of n-(9-anthroyloxy) fatty acids (n = 2, 6, 9, 12 and 16) whose fluorophore is located at a graded series of depths from the surface to the centre of the bilayer. The results show that DDT is a fluidizer of DPPC and egg PC bilayers. The increase in microviscosity of DPPC bilayers at 23°C begins at the centre of the bilayer (5 mol% DDT) and proceeds outward to the surface with increasing concentration of DDT (17 mol%). This pattern of effects is not evident in fluid bilayers of DPPC at 54°C or egg PC at 23°C. DDT (33 mol%) also lowers the phase transition temperature of DPPC bilayers by approximately 2 Cdeg. DDT (17 mol%) had no effect on the mean excited fluorescence life-time of 2-AP and 12-AS in DPPC, DOPC and egg PC bilayers. No quenching of 2-AP fluorescence was evident.     

Alamethicin in lipid bilayers: Combined use of X-ray scattering and MD simulations

We study fully hydrated bilayers of two di-monounsaturated phospholipids diC18:1PC (DOPC) and diC22:1PC with varying amounts of alamethicin (Alm). We combine the use of X-ray diffuse scattering and molecular dynamics simulations to determine the orientation of alamethicin in model lipids. Comparison of the experimental and simulated form factors shows that Alm helices are inserted transmembrane at high humidity and high concentrations, in agreement with earlier results. The X-ray scattering data and the MD simulations agree that membrane thickness changes very little up to 1/10 Alm/DOPC. In contrast, the X-ray data indicate that the thicker diC22:1PC membrane thins with added Alm, a total decrease in thickness of 4 Å at 1/10 Alm/diC22:1PC. The different effect of Alm on the thickness changes of the two bilayers is consistent with Alm having a hydrophobic thickness close to the hydrophobic thickness of 27 Å for DOPC; Alm is then mismatched with the 7 Å thicker diC22:1PC bilayer. The X-ray data indicate that Alm decreases the bending modulus (K_C) by a factor of ∼ 2 in DOPC and a factor of ∼ 10 in diC22:1PC membranes (P/L ∼ 1/10). The van der Waals and fluctuational interactions between bilayers are also evaluated through determination of the anisotropic B compressibility modulus.     

Small phosphatidylcholine vesicles appear to be faceted below the thermal phase transition

Summary We have studied the main thermal transition in dipalmitoyl phosphatidylcholine (DPPC) multilayers and a similar transition in small (300 Å diameter), single-walled vesicles by X-ray diffraction. As judged by the large-angle diffraction, the transition in the multilayers is narrow; aside from small tails, the transition occurs over a range of 0.5°C. In contrast, the transition in the vesicles is quite broad; the range is about 7°C. These observations are in agreement with recently published data.Referring to the small vesicles below the thermal transition, a bilayer structure in which the C₁₆ chains are all straight and pointed radially is inconsistent with the large-angle diffraction. Assuming instead that the chains are packed in a regular, planar array, it is clear from their small size that the vesicles can have only limited regions of planar packing. The X-ray data indicate that the planar regions are 75 Å across on the average. In view of the 75-Å size and the average vesicle diameter of about 300 Å, we propose that the small vesicles are faceted below the transition, i.e., that the vesicles are polygonal. The small-angle diffraction pattern from the vesicles below the transition provides support for the faceted structure.     

Structural investigation of porcine stomach mucin by X-ray fiber diffraction and homology modeling

The basic understanding of the three dimensional structure of mucin is essential to understand its physiological function. Technology has been developed to achieve orientated porcine stomach mucin molecules. X-ray fiber diffraction of partially orientated porcine stomach mucin molecules show d-spacing signals at 2.99, 4.06, 4.22, 4.7, 5.37 and 6.5 Å. The high intense d-spacing signal at 4.22 Å is attributed to the antiparallel β-sheet structure identified in the fraction of the homology modeled mucin molecule (amino acid residues 800–980) using Nidogen–Laminin complex structure as a template. The X-ray fiber diffraction signal at 6.5 Å reveals partial organization of oligosaccharides in porcine stomach mucin. This partial structure of mucin will be helpful in establishing a three dimensional structure for the whole mucin molecule.     

Influence of Cholesterol and ��-Sitosterol on the Structure of EYPC Bilayers

The influence of cholesterol and β-sitosterol on egg yolk phosphatidylcholine (EYPC) bilayers is compared. Different interactions of these sterols with EYPC bilayers were observed using X-ray diffraction. Cholesterol was miscible with EYPC in the studied concentration range (0-50 mol%), but crystallization of β-sitosterol in EYPC bilayers was observed at X ≥ 41 mol% as detected by X-ray diffraction. Moreover, the repeat distance (d) of the lamellar phase was similar upon addition of the two sterols up to mole fraction 17%, while for X ≥ 17 mol% it became higher in the presence of β-sitosterol compared to cholesterol. SANS data on suspensions of unilamellar vesicles showed that both cholesterol and β-sitosterol similarly increase the EYPC bilayer thickness. Cholesterol in amounts above 33 mol% decreased the interlamellar water layer thickness, probably due to "stiffening" of the bilayer. This effect was not manifested by β-sitosterol, in particular due to the lower solubility of β-sitosterol in EYPC bilayers. Applying the formalism of partial molecular areas, it is shown that the condensing effect of both sterols on the EYPC area at the lipid-water interface is small, if any. The parameters of ESR spectra of spin labels localized in different regions of the EYPC bilayer did not reveal any differences between the effects of cholesterol and β-sitosterol in the range of full miscibility.     

Asymmetric structural features in single supported lipid bilayers containing cholesterol and GM1 resolved with synchrotron X-Ray reflectivity

The cell membrane comprises numerous protein and lipid molecules capable of asymmetric organization between leaflets and liquid-liquid phase separation. We use single supported lipid bilayers (SLBs) to model cell membranes, and study how cholesterol and asymmetrically oriented ganglioside receptor G_M1 affect membrane structure using synchrotron x-ray reflectivity. Using mixtures of cholesterol, sphingomyelin, and 1,2-dioleoyl-sn-glycero-3-phosphocholine, we characterize the structure of liquid-ordered and liquid-disordered SLBs in terms of acyl-chain density, headgroup size, and leaflet thickness. SLBs modeling the liquid-ordered phase are 10 Å thicker and have a higher acyl-chain electron density (〈ρ_chain〉 = 0.33 e⁻/ų) compared to SLBs modeling the liquid-disordered phase, or pure phosphatidylcholine SLBs (〈ρ_chain〉 = 0.28 e⁻/ų). Incorporating G_M1 into the distal bilayer leaflet results in membrane asymmetry and thickening of the leaflet of 4-9 Å. The structural effect of G_M1 is more complex in SLBs of cholesterol/sphingomyelin/1,2-dioleoyl-sn-glycero-3-phosphocholine, where the distal chains show a high electron density (〈ρ_chain〉 = 0.33 e⁻/ų) and the lipid diffusion constant is reduced by ∼50%, as measured by fluorescence microscopy. These results give quantitative information about the leaflet asymmetry and electron density changes induced by receptor molecules that penetrate a single lipid bilayer.     

Ceramide-1-Phosphate, in Contrast to Ceramide, Is Not Segregated into Lateral Lipid Domains in Phosphatidylcholine Bilayers

Sphingolipids are key lipid regulators of cell viability: ceramide is one of the key molecules in inducing programmed cell death (apoptosis), whereas other sphingolipids, such as ceramide 1-phosphate, are mitogenic. The thermotropic and structural behavior of binary systems of N-hexadecanoyl-D-erythro-ceramide (C₁₆-ceramide) or N-hexadecanoyl-D-erythro-ceramide-1-phosphate (C₁₆-ceramide-1-phosphate; C₁₆-C1P) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was studied with DSC and deuterium nuclear magnetic resonance (²H-NMR). Partial-phase diagrams (up to a mole fraction of sphingolipids X = 0.40) for both mixtures were constructed based on DSC and ²H-NMR observations. For C₁₆-ceramide-containing bilayers DSC heating scans showed already at X_cer = 0.025 a complex structure of the main-phase transition peak suggestive of lateral-phase separation. The transition width increased significantly upon increasing X_cer, and the upper-phase boundary temperature of the mixture shifted to ∼65°C at X_cer = 0.40. The temperature range over which ²H-NMR spectra of C₁₆-ceramide/DPPC-d₆₂ mixtures displayed coexistence of gel and liquid crystalline domains increased from ∼10° for X_cer = 0.1 to ∼21° for X_cer = 0.4. For C16-C1P/DPPC mixtures, DSC and ²H-NMR observations indicated that two-phase coexistence was limited to significantly narrower temperature ranges for corresponding C1P concentrations. To complement these findings, C₁₆-ceramide/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and C16-C1P/POPC mixtures were also studied by ²H-NMR and fluorescence techniques. These observations indicate that DPPC and POPC bilayers are significantly less perturbed by C₁₆-C1P than by C₁₆-ceramide and that C₁₆-C1P is miscible within DPPC bilayers at least up to X_C1P = 0.30.     

Molecular dynamics study of changes in physico-chemical properties of DMPC lipid bilayers by addition of nonionic surfactant C12E10

Changes in physico-chemical properties of dimyristoyl phosphatidylcholine (DMPC) lipid bilayers caused by the addition of 9.4 mol% nonionic surfactant decaoxyethylene monododecyl ethers (C₁₂E₁₀) have been investigated by molecular dynamics calculations. In spite of addition of single chain C₁₂E₁₀, the lipid bilayers showed an increase of membrane area. Isothermal area compressibility, which is a measure of membrane softness in lateral direction, also increased by 50% for DMPC/C₁₂E₁₀ mixed bilayers. Furthermore, the order parameter of C–H vector for DMPC acyl tails decreased. We found that these changes are caused by the hydrophilic head groups of C₁₂E₁₀ which are located near the glycerol backbone of the DMPC molecules and have bulky random coil conformation without any preferential ordered structures.     

Investigation of the adsorption of PEG1500-12-acyloxystearate surfactants onto phospholipid bilayers: an ellipsometry and cryo-TEM study

In this article we present a study of a new class of surfactants denoted as PEG1500-12-acyloxystearates, which have potential use as pharmaceutical solubilizers. These amphiphilic molecules present interesting properties with regard to cell damage effects. PEG1500-12-acyloxystearates with C₁₄ to C₁₆ acyloxy chains cause little or no damage to red blood and intestinal cells, whereas the surfactants with shorter chains, from C₈ to C₁₂, induce measurable damage. To start unraveling the reason why there is this rather marked dependence of the cell damage effect on surfactant chain length, we have carried out systematic studies of adsorption properties of the surfactants onto phospholipid bilayers by means of ellipsometry. The rate of incorporation of the surfactants in the lipid membrane decreases with increasing length of the acyloxy chain. Cryo-TEM images strengthen the ellipsometry results by showing that the dissolution of the phospholipid bilayer is slower for the surfactants of the series having longer chains.