Methotrexate interaction with a lipid membrane model of DPPC

Dipalmitoylphosphatidylcholine (DPPC) liposomes were employed as membrane models for the investigation of the interaction occurring between methotrexate (MTX) and bilayer lipid matrix. Liposomes were obtained by hydrating a lipid film with 50 mM Tris buffer (pH 7.4). The differential scanning calorimetry (DSC) evaluation of the thermotropic parameters associated with the phase transitions of DPPC liposomes gave useful information about the kind of drug-membrane interaction. The results showed an electrostatic interaction taking place with the negatively charged molecules of MTX and the phosphorylcholine head groups, constituting the outer part of DPPC bilayers. No interaction with the hydrophobic phospholipid bilayer domains was detected, revealing a poor capability of MTX to cross through lipid membranes to reach the interior compartment of a lipid bounded structure. These findings correlate well within vitro biological experiments on MTX cell susceptibility.     

Binding of nonsteroidal anti-inflammatory drugs to DPPC: structure and thermodynamic aspects

The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the phase transition and phase properties of 1,2-dipalmitoylphosphatidylcholine (DPPC) has been investigated in both 2D (monolayers at the air/water interface) and 3D (multilayers in lipid/water dispersions) model systems. The 2D membrane models have been characterized by means of pressure-area isotherms and grazing incidence X-ray diffraction (GIXD) measurements. Differential scanning calorimetry (DSC) and simultaneous small- and wide-angle X-ray diffraction have been applied to lipid aqueous dispersions. All NSAIDs studied altered the main transition temperature of the gel to liquid-crystalline phase transition, with the arylacetic acid derivatives (acemetacin and indomethacin) showing the largest effects. A comparison of the results reveals distinct structural features of the membrane models after interaction with the NSAID. All drugs induced perturbations in the lipid liquid-crystalline phase, suggesting a major change in the hydration behavior of DPPC. Again, the largest effects on the structural parameters are found for the arylacetic acid derivatives. The results obtained in the different model systems give indications of the role of the membrane/NSAID interactions that might also be important for NSAID gastric injury.     

Nanoscale imaging of domains in supported lipid membranes

The formation of domains in supported lipid membranes has been studied extensively as a model for the 2D organization of cell membranes. The compartmentalization of biological membranes to give domains such as cholesterol-rich rafts plays an important role in many biological processes. This article summarizes experiments from the author's laboratory in which a combination of atomic force microscopy and near-field scanning optical microscopy is used to probe phase separation in supported monolayers and bilayers as models for membrane rafts. These techniques are used to study binary and ternary lipid mixtures that have gel-phase or liquid-ordered domains that vary in size from tens of nanometers to tens of micrometers, surrounded by a fluid-disordered membrane. Examples are presented in which these models are used to investigate the distribution of glycolipid membrane raft markers and the preference for peptide and protein localization in ordered versus fluid membrane phases. Finally, the enzyme-mediated restructuring of membranes containing liquid-ordered domains provides an in vitro model for the coalescence of membrane rafts to give signaling platforms. Overall, the results demonstrate the importance of using techniques that can probe the nanoscale organization of membranes and of combining techniques that yield complementary information. Furthermore, the ability of supported lipid bilayers to model some aspects of membrane compartmentalization provides an important approach to understanding natural membranes.     

Interactions in lipid stabilised foam films

The interaction between lipid bilayers in water has been intensively studied over the last decades. Osmotic stress was applied to evaluate the forces between two approaching lipid bilayers in aqueous solution. The force–distance relation between lipid mono- or bilayers deposited on mica sheets using a surface force apparatus (SFA) was also measured. Lipid stabilised foam films offer another possibility to study the interactions between lipid monolayers. These films can be prepared comparatively easy with very good reproducibility. Foam films consist usually of two adsorbed surfactant monolayers separated by a layer of the aqueous solution from which the film is created. Their thickness can be conveniently measured using microinterferometric techniques. Studies with foam films deliver valuable information on the interactions between lipid membranes and especially their stability and permeability. Presenting inverse black lipid membrane (BLM) foam films supply information about the properties of the lipid self-organisation in bilayers. The present paper summarises results on microscopic lipid stabilised foam films by measuring their thickness and contact angle. Most of the presented results concern foam films prepared from dispersions of the zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and some of its mixtures with the anionic lipid — 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG).     

Molecular dynamics simulations of rhodopsin in different one-component lipid bilayers

Four 20 ns molecular dynamic simulations of rhodopsin embedded in different one-component lipid bilayers have been carried out to ascertain the importance of membrane lipids on the protein structure. Specifically, dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), palmitoyl oleoyl phosphatidylcholine (POPC), and palmitoyl linoleyl phosphatidylcholine (PLPC) lipid bilayers have been considered for the present work. The results reported here provide information on the hydrophobic matching between the protein and the bilayer and about the differential effects of the protein on the thickness of the different membranes. Furthermore, a careful analysis of the individual protein-lipid interactions permits the identification of residues that exhibit permanent interactions with atoms of the lipid environment that may putatively act as hooks of the protein to the membrane. The analysis of the trajectories also provides information about the effect of the bilayer on the protein structure, including secondary structural elements, salt bridges, and rigid-body motions.     

Immobilized phospholipid capillary electrophoresis for study of drug-membrane interactions and prediction of drug activity

Immobilized phospholipid capillary electrophoresis (IPCE) was developed for studying the interactions between a set of nonsteroidal anti-inflammatory drugs (NSAIDs) and membrane and predicting the biological activity of NSAIDs. Supported vesicle layers and supported phospholipid bilayers were attached to the inner surface of a capillary wall simply by rinsing with liposome solutions. The liposomes, composed of soybean phosphatidylcholine (SPC) or SPC and different proportions of cholesterol (Ch), were small unilamellar vesicles prepared by sonication. The normalized capacity factor (K(IPCE)) was introduced into IPCE for evaluating drug-membrane interactions. Related theories and equations were derived to calculate K(IPCE) values from apparent migration time of a solute and electroosmotic flow. The strong relationships were observed between logK(IPCE) (SPC) values and logK(lw) values (the partition coefficients determined in free SPC-liposome partitioning system) (R=0.9855 and P<0.0001) or logK(ILC) values (the normalized capacity factors determined by immobilized POPC-liposome chromatography, POPC represents 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) (R=0.9875 and P<0.0001). In addition, logK(IPCE) (SPC/Ch 80:20%) values correlated well with the pIC50 (the minus logarithm of IC50) values for cyclooxygenase 2 determined on intact cells (R=0.959 and P<0.001). These results confirmed that IPCE, K(IPCE) value as evaluation index, can be effectually used for studying drug-membrane interactions and it has the potential to predict drug activity. Cholesterol-containing (20 mol%) liposomes may be more suitable to mimic real cell membrane.     

Fusogenic tilted peptides induce nanoscale holes in supported phosphatidylcholine bilayers

Tilted peptides are known to insert in lipid bilayers with an oblique orientation, thereby destabilizing membranes and facilitating membrane fusion processes. Here, we report the first direct visualization of the interaction of tilted peptides with lipid membranes using in situ atomic force microscopy (AFM) imaging. Phase-separated supported dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DOPC/DPPC) bilayers were prepared by fusion of small unilamellar vesicles and imaged in buffer solution, in the absence and in the presence of the simian immunodeficiency virus (SIV) peptide. The SIV peptide was shown to induce the rapid appearance of nanometer scale bilayer holes within the DPPC gel domains, while keeping the domain shape unaltered. We attribute this behavior to a local weakening and destabilization of the DPPC domains due to the oblique insertion of the peptide molecules. These results were directly correlated with the fusogenic activity of the peptide as determined using fluorescently labeled DOPC/DPPC liposomes. By contrast, the nontilted ApoE peptide did not promote liposome fusion and did not induce bilayer holes but caused slight erosion of the DPPC domains. In conclusion, this work provides the first direct evidence for the production of stable, well-defined nanoholes in lipid bilayer domains by the SIV peptide, a behavior that we have shown to be specifically related to the tilted character of the peptide. A molecular mechanism underlying spontaneous insertion of the SIV peptide within lipid bilayers and the subsequent removal of bilayer patches is proposed, and its relevance to membrane fusion processes is discussed.     

Fengycin interaction with lipid monolayers at the air-aqueous interface-implications for the effect of fengycin on biological membranes

In this study, we investigated the interaction of fengycin, a lipopeptide produced by Bacillus subtilis, with lipid monolayers using the Langmuir trough technique in combination with Brewster angle microscopy. Thermodynamic analyses were performed to get further information about the mixing behavior and the molecular interactions between the two components. The effect of fengycin on the structural and morphological characteristics of DPPC monolayers, as a simple model of biological membranes, depends on the fengycin molar ratio. With a small proportion of fengycin (X(f)0.1), the compressibility of the monolayer is modified but the morphological characteristics of the DPPC are not significantly affected. At an intermediate molar ratio (0.1相似文献   

Ceramide-enriched microdomains in planar membranes

Ceramide has a large effect on the properties of biological membranes, increasing lipid order and promoting lateral phase separation, and plays an important role in cell signaling. This review provides an overview of recent studies of the effects of direct ceramide incorporation and enzymatic ceramide generation on planar supported membranes, including lipid monolayers and supported lipid bilayers. Recent studies have focused on understanding the nucleation, growth and morphology of ceramide gel domains, characterizing the properties of ceramide-rich membrane phases and investigating the effects of ceramide on phase-separated membranes with co-existing liquid-ordered and fluid phases, as models for cellular membranes.     

Phospholipids Bilayers as Molecular Models for Drug- Membrane Interactions. The Case of the Antiepileptics Phenytoin and Carbamazepine

With the aim to better understand the molecular mechanisms of the interaction of phenytoin and carbamazepine with cell membranes we utilized a well-established model consisting in intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of its membrane. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidyl-ethanolamine (DMPE), representative of phospholipid classes respectively located in the outer and inner monolayers of erythrocytes and other cell membranes. This report presents the following evidence that phenytoin and carbamazepine interact with membrane phospholipids: a) X-ray diffraction and fluorescence spectroscopy showed that both drugs preferentially interacted with DMPC; b) in IUM, the drugs induced a disordering effect on the polar head groups and acyl chains of the eryhrocyte membrane lipid bilayers; c) electron microscopy observations of human erythrocytes showed the echinocyte formation, an effect due to phenytoin and carbamazepine insertion in the outer monolayer of the red cell membrane.     

Influence of perfluorinated compounds on the properties of model lipid membranes

The influence of selected perfluorinated compounds (PFCs), perfluorooctanoic acid (PFOA) or perfluorooctanesulfonic acid (PFOS), on the structure and organization of lipid membranes was investigated using model membranes-lipid monolayers and bilayers. The simplest model--a lipid monolayer--was studied at the air-water interface using the Langmuir-Blodgett technique with surface pressure and surface potential measurements. Lipid bilayers were characterized by NMR techniques and molecular dynamics simulations. Two phospholipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), characterized by different surface properties have been chosen as components of the model membranes. For a DPPC monolayer, a phase transition from the liquid-expanded state to the liquid-condensed state can be observed upon compression at room temperature, while a DMPC monolayer under the same conditions remains in the liquid-expanded state. For each of the two lipids, the presence of both PFOA and PFOS leads to the formation of a more fluidic layer at the air-water interface. Pulsed field gradient NMR measurements of the lateral diffusion coefficient (DL) of DMPC and PFOA in oriented bilayers reveal that, upon addition of PFOA to DMPC bilayers, DL of DMPC decreases for small amounts of PFOA, while larger additions produce an increased DL. The DL values of PFOA were found to be slightly larger than those for DMPC, probably as a consequence of the water solubility of PFOA. Furthermore, 31P and 2H NMR showed that the gel-liquid crystalline phase transition temperature decreased by the addition of PFOA for concentrations of 5 mol % and above, indicating a destabilizing effect of PFOA on the membranes. Deuterium order parameters of deuterated DMPC were found to increase slightly upon increasing the PFOA concentration. The monolayer experiments reveal that PFOS also penetrates slowly into already preformed lipid layers, leading to a change of their properties with time. These experimental observations are in qualitative agreement with the computational results obtained from the molecular dynamics simulations showing a slow migration of PFCs from the surrounding water phase into DPPC and DMPC bilayers.     

Membrane interactions of host-defense peptides studied in model systems

Host-defense, antibiotic peptides are believed to generate their cytolytic effects by interacting with the membranes of bacterial cells. Direct analyses of peptide interactions with real cellular membranes are difficult, however, due to the high complexity of physiological membranes. This review summarizes experimental work aiming to understand peptide-membrane interactions and their relationships with the peptides' biological actions using specific model systems. Varied model assemblies have been constructed that generally aim to mimic the fundamental lipid bilayer organization of the membrane. The model systems we will describe include multilamellar and unilamellar vesicles, planar lipid bilayers, lipid monolayers and micelles, and colorimetric biomimetic membranes. The different artificial models have facilitated examination of specific biological or chemical parameters affecting peptide action, for example the effect of membrane lipid composition on peptide affinities and membrane penetration, the relationship between membrane fluidity and peptide interactions, the conformations of active peptides, and other factors. We evaluate the strengths and limitations of the various approaches, and point to future directions in the field.     

Effects of lipid chain unsaturation and headgroup type on molecular interactions between paclitaxel and phospholipid within model biomembrane

Molecular interactions between paclitaxel, an anticancer drug, and phospholipids of various chain unsaturations and headgroup types were investigated in the present study by Langmuir film balance and differential scanning calorimetry. Both the lipid monolayer at the air-water interface and the lipid bilayer vesicles (liposomes) were employed as model cell membranes. It was found that, regardless of the difference in molecular structure of the lipid chains and headgroup, the drug can form nonideal, miscible systems with the lipids at the air-water interface over a wide range of paclitaxel mole fractions. The interaction between paclitaxel and phospholipid within the monolayer was dependent on the molecular area of the lipids at the interface and can be explained by intermolecular forces or geometric accommodation. Paclitaxel is more likely to form thermodynamically stable systems with 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) and 1,2-dielaidoyl-sn-glycero-3-phosphocholine (DEPC) than with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Investigation of the drug penetration into the lipid monolayer showed that DPPC and DEPC have higher incorporation abilities for the drug than DPPE and DSPC. A similar trend was also evidenced by DSC investigation with liposomes. While little change of DSC profiles was observed for the DPPE/paclitaxel and DSPC/paclitaxel liposomes, paclitaxel caused noticeable changes in the thermographs of DPPC and DEPC liposomes. Paclitaxel was found to cause broadening of the main phase transition without significant change in the peak melting temperature of the DPPC bilayers, which demonstrates that paclitaxel was localized in the outer hydrophobic cooperative zone of the bilayer, i.e., in the region of the C1-C8 carbon atoms of the acyl chain or binding at the polar headgroup site of the lipids. However, it may penetrate into the deeper hydrophobic zone of the DEPC bilayers. These findings provide useful information for liposomal formulation of anticancer drugs as well as for understanding drug-cell membrane interactions.     

Investigation of the interactions of lupane type pentacyclic triterpenes with outer leaflet membrane phospholipids--Langmuir monolayer and synchrotron X-ray scattering study

Lupane type pentacyclic triterpenes (LTs) are pharmacologically active natural products isolated from different plants. They have broad spectrum of therapeutic action ranging from anticancer via anti-HIV, antibiotic to anti-inflammatory and anti-protozoal activity. Many scientific papers underline that the key stage in the LT mechanism of action is their incorporation into cellular membrane and the interaction with the structural lipids. In our research we apply Langmuir monolayers as a versatile platform for the investigation of these phenomena, since till now important aspects concerning this issue are incomprehensible. We focus our attention on the interactions of lupeol and betulinic acid with choline-headgroup structural lipids: a representative of saturated glycerophosphatidylcholines (DPPCs), and octadecyl-sphingomyelin--a representative of membrane sphingolipids. Application of complementary physicochemical techniques such as the Langmuir technique, Brewster angle microscopy, and grazing incidence X-ray diffraction supported by thermodynamic analysis enabled us to investigate the intermolecular interactions in such binary model systems. Our results corroborate that LT is miscible with the outer leaflet membrane phospholipids, both DPPC and SM in the whole range of mole ratios. Moreover, the introduction of LT into the phospholipid film, even in small proportion, leads to the loss of periodical ordering of the phospholipid molecules and the disappearance of the diffraction signal as observed by GIXD. Our results also proved that LT does not form any surface complexes of fixed stoichiometry resembling the well characterized lipid rafts.     

Synthesis and physicochemical study of the laminin active sequence: SIKVAV

The synthesis, physicochemical characterization, and interaction with membrane model systems of a peptide derived from the PA22-2 region of laminin are described. Surface activity studies indicate that this peptide is able to spread at the air-water interface being the maximal spreading pressure 20 mN/m at subphase concentrations around 10 micro M. Besides, these peptide molecules are also able to form stable monolayers. Physicochemical studies concerning the interaction of this peptide with lipids, organized in mono and bilayers, were carried out using Langmuir balance experiments and polarization fluorescence techniques. The peptide penetrates better in monolayers of DPPC than in those of PC and forms condensed mixed monolayers with DPPC. Energies of mixing are small thus indicating that deviations from ideality were almost negligible. Interactions with bilayers were studied through microviscosity changes (DPH and TMA-DPH probes), membrane permeability alterations (CF, NBD-PE/dithionite), and fusion promotion (NBD-PE/Rh-PE, resonance energy transfer). Results indicate that this sequence interacts very softly with bilayers without promoting changes in their organization. These data as well as the lack of interaction with erythrocytes suggest that coating liposomes with this peptide through chemical amide bonds can render stable inmunoliposomes for further biological applications.     

Supported lipid bilayers lifted from the substrate by layer-by-layer polyion cushions on self-assembled monolayers

The formation of lipid bilayers, lifted from the solid substrate by layer-by-layer polyion cushions, on self-assembled monolayers (SAMs) on gold was investigated by surface plasmon resonance (SPR) and fluorescence recovery after photobleaching (FRAP). The polyions poly(diallyldimethylammonium chloride) (PDDA) and polystyrene sulfonate (PSS) sodium salt were used for the layer-by-layer polyion macromolecular assembly. The cushion was formed by electrostatic interaction of PDDA/PSS/PDDA layers with a negatively charged surface of an SAM of 11-mercaptoundecanoic acid (MUA) on gold. The lipid bilayer membranes were deposited by vesicle fusion with different compositions of SOPS (an anionic lipid, 1-stearoyl-2-oleoyl-phosphatidylserine) and POPC (a zwitterionic lipid, 1-palmitoyl-2-oleoylphosphatidylcholine). In the case of pure SOPS and for lipid mixtures with a POPC composition up to 25%, single bilayers were deposited. FRAP experiments showed that single bilayers supported on PDDA/PSS/PDDA/MUA were mobile at room temperature, with lateral coefficients of approximately (1.2–2.1)×10⁻⁹ cm²/s. The kinetics of the addition of the ion-channel-forming peptide protegrin-1 to the supported bilayers was detected by SPR. A two-step interaction was observed, similar to the association behavior of protegrin-1 with bilayers supported on PDDA/MUA. The results are similar to that of supported lipid bilayers without a layer-by-layer cushion. The model membrane system in this work is a potential biosensor for mimicking the natural activities of biomolecules and is a possible tool to investigate the fundamental properties of biomembranes.     

Composition and asymmetry in supported membranes formed by vesicle fusion

The structure and formation of supported membranes at silica surfaces by vesicle fusion was investigated by neutron reflectivity and quartz crystal microbalance (QCM-D) measurements. The structure of equimolar phospholipid mixtures of DLPC-DPPC, DMPC-DPPC, and DOPC-DPPC depends intricately on the vesicle deposition conditions. The supported bilayer membranes exhibit varying degrees of compositional asymmetry between the monolayer leaflets, which can be modified by the deposition temperature as well as the salt concentration of the vesicle solution. The total lipid composition of the supported bilayers differs from the composition of the vesicles in solution, and the monolayer proximal to the silica surface is always enriched in DPPC compared to the distal monolayer. The results, which show unambiguougsly that some exchange and rearrangement of lipids occur during vesicle deposition, can be rationalized by considering the effects of salt screening and temperature on the rates of lipid exchange, rearrangement, and vesicle adsorption, but there is also an intricate dependence on the lipid-lipid interactions. Thus, although both symmetric and asymmetric supported bilayers can be prepared from vesicles, the optimal conditions are sensitive to the lipid composition of the system.     

Filipin orientation revealed by linear dichroism. Implication for a model of action

The organization of the polyene antibiotic filipin in membranes containing cholesterol is a controversial matter of debate. Two contradictory models exist, one suggesting a parallel and the other perpendicular organization of filipin with respect to the plane of the membrane. UV-vis linear dichroism, ATR-FTIR, and fluorescence anisotropy decay techniques were combined to study the orientation of filipin in model systems of membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) with and without cholesterol. Filipin's orientation is determined by the presence/absence of cholesterol when it is inserted in gel crystalline phase model membranes. When cholesterol (33%) is present in DPPC bilayers, filipin stands perpendicular to the membrane surface as expected in "pore-forming" models. At variance, absence of cholesterol leaves filipin in an essentially random organization in the lipidic matrix. In liquid crystalline phase bilayers (POPC) filipin's orientation is perpendicular to the membrane surface even in absence of cholesterol. Thus filipin's activity/organization depends not only on cholesterol presence but also in the lipid phase domain it is inserted in. These findings were combined with spectroscopy and microscopy data in the literature, solving controversial matters of debate.     

Long-range Lennard-Jones and electrostatic interactions in interfaces: application of the isotropic periodic sum method

Molecular dynamics (MD) simulations of heptane/vapor, hexadecane/vapor, water/vapor, hexadecane/water, and dipalmitoylphosphatidylcholine (DPPC) bilayers and monolayers are analyzed to determine the accuracy of treating long-range interactions in interfaces with the isotropic periodic sum (IPS) method. The method and cutoff (rc) dependences of surface tensions, density profiles, water dipole orientation, and electrostatic potential profiles are used as metrics. The water/vapor, heptane/vapor, and hexadecane/vapor interfaces are accurately and efficiently calculated with 2D IPS (rc=10 A). It is demonstrated that 3D IPS is not practical for any of the interfacial systems studied. However, the hybrid method PME/IPS [Particle Mesh Ewald for electrostatics and 3D IPS for Lennard-Jones (LJ) interactions] provides an efficient way to include both types of long-range forces in simulations of large liquid/vacuum and all liquid/liquid interfaces, including lipid monolayers and bilayers. A previously published pressure-based long-range LJ correction yields results similar to those of PME/IPS for liquid/liquid interfaces. The contributions to surface tension of LJ terms arising from interactions beyond 10 A range from 13 dyn/cm for the hexadecane/vapor interface to approximately 3 dyn/cm for hexadecane/water and DPPC bilayers and monolayers. Surface tensions of alkane/vapor, hexadecane/water, and DPPC monolayers based on the CHARMM lipid force fields agree very well with experiment, whereas surface tensions of the TIP3P and TIP4P-Ew water models underestimate experiment by 16 and 11 dyn/cm, respectively. Dipole potential drops (DeltaPsi) are less sensitive to long-range LJ interactions than surface tensions. However, DeltaPsi for the DPPC bilayer (845+/-3 mV proceeding from water to lipid) and water (547+/-2 mV for TIP4P-Ew and 521+/-3 mV for TIP3P) overestimate experiment by factors of 3 and 5, respectively, and represent expected deficiencies in nonpolarizable force fields.     

Interaction of the Hepatitis A peptide VP3(110–121) with lipid mono and bilayer models of cellular membranes

 The surface activity of HAV-VP3(110–121) peptide was studied at different concentrations in an aqueous solution. Saturation was reached at 0.62 μM concentration. The ability of the peptide to insert into monolayers of CL, SA, DPPC, DPPC/5% CL and DPPC/5% SA was also performed. Mixed mono-layers composed of this peptide and the lipid mixtures were also studied as far as the miscibility of the two components is concerned. The mixed monolayers showing small negative deviations from ideality. The values of excess free energy of mixing (ΔG ^E _M) suggest that the energy associated to the miscibility process is almost non-significant except for a 0.2 molar fraction of DPPC/SA and 0.6 molar fraction of DPPC/CL. The peptide has an expanding effect upon the monolayers but due to its amphoteric character this interaction is not dependent on the electrical charge of the lipids. In fluorescence studies, the peptide showed some degree of interaction with the lipid polar heads, but no interactions were detected with its alkylchains. This results show that after incubation with DPPC/5% CL and DPPC/5% SA liposomes the peptide remains in the outer part of the bilayers. Received: 20 January 1997 Accepted: 28 May 1997