Phospholipid membranes are ubiquitous components of cells involved in physiological processes; thus, knowledge regarding their interactions with other molecules, including tocopherol ester derivatives, is of great importance. The surface pressure–area isotherms of pure α-tocopherol (Toc) and its derivatives (oxalate (OT), malonate (MT), succinate (ST), and carbo analog (CT)) were studied in Langmuir monolayers in order to evaluate phase formation, compressibility, packing, and ordering. The isotherms and compressibility results indicate that, under pressure, the ester derivatives and CT are able to form two-dimensional liquid-condensed (LC) ordered structures with collapse pressures ranging from 27 mN/m for CT to 44 mN/m for OT. Next, the effect of length of ester moiety on the surface behavior of DPPC/Toc derivatives’ binary monolayers at air–water interface was investigated. The average molecular area, elastic modulus, compressibility, and miscibility were calculated as a function of molar fraction of derivatives. Increasing the presence of Toc derivatives in DPPC monolayer induces expansion of isotherms, increased monolayer elasticity, interrupted packing, and lowered ordering in monolayer, leading to its fluidization. Decreasing collapse pressure with increasing molar ratio of derivatives indicates on the miscibility of Toc esters in DPPC monolayer. The interactions between components were analyzed using additivity rule and thermodynamic calculations of excess and total Gibbs energy of mixing. Calculated excess area and Gibbs energy indicated repulsion between components, confirming their partial mixing. In summary, the mechanism of the observed phenomena is mainly connected with interactions of ionized carboxyl groups of ester moieties with DPPC headgroup moieties where formed conformations perturb alignment of acyl chains, resulting in increasing mean area per molecule, leading to disordering and fluidization of mixed monolayer. 相似文献
Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660?cm?1) and Amide II band (at about 1546?cm?1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule. 相似文献
Summary DPPC dispersions containing DPPE with attached PEG of molecular masses 350, 2000 and 5000 were investigated by DSC in order to determine their phase behaviour and potential use as drug delivery systems. In comparison with previously obtained ESR data, DSC provided a definition of the lipid composition and temperature at which the vesicles are in a liquid crystalline phase. For DPPC DPPE-PEG 350 the composition range is at molar fractions 0<&khgr;PEG350<0.5.For DPPC DPPE-PEG 2000 the range of applicability is 0<&khgr;PEG2000<0.07 and for DPPC/DPPE-PEG 5000 system it is 0<&khgr;PEG5000<0.05. 相似文献
Summary DSC and EPR experiments were performed on human erythrocyte membranes and DPPC vesicles in order to study the effect of the
anaesthetic drug tetracaine on structure and dynamics of the lipid region. Experiments using spin label technique showed that
tetracaine induced fluidity changes of the lipid region in the environment of the fatty acid probe molecules incorporated
into the membranes in the vicinity of the lipid-water interface. Similarly to EPR observations, DSC measurements reported
decrease of the main melting and the pretransition temperature in comparison to control DPPC vesicles, which is the sign of
destabilisation of the structure in the head group region of the lipids. Similar effect was observed in the case of erythrocytes
where the protein conformation was also controlled in the presence of drug. A separated membrane melting with well distinguished
membrane protein phase transition was found that was affected significantly by tetracaine. These results suggest that tetracaine
is able to modify not only the internal dynamics of erythrocyte membranes and produce destabilisation of the lipid structure,
but the protein system as well. These might lead to further damage of the biological functions. 相似文献
The thermotropic behavior of dipalmitoylphosphatidylcholine (DPPC) multibilayers containing up to 10 mol% of lyso-palmitoylphosphatidylcholine
(lyso-PPC) with and without low content of poly(ethylene glycol:2000)-grafted dipalmitoylphosphatidylethanolamine (PEG:2000-DPPE)
has been studied by high sensitivity differential scanning calorimetry (DSC) and electron spin resonance (ESR) using the spin
probe di-tert-butyl-nitroxide (DTBN). The three lipids, dispersed in buffer at appropriate concentrations, form thermosensitive liposomes
used as site-specific drug-delivery systems. Without polymer–lipids, the DPPC main transition temperature is downshifted of
1.2–1.3 °C at the highest lyso-PPC content. The molar enthalpy and the cooperative unit of the DPPC main transition first
decrease rapidly, then more slowly and finally slightly increase with lyso-PPC content. Moreover, in the mixed dispersions,
the membrane fluidity increases at any temperature. The addition up to 5 mol% of PEG:2000-DPPE to DPPC/10 mol% lyso-PPC mixtures
does not affect neither the thermotropic phase behavior nor the transition cooperativity and the fluidity of the dispersions. 相似文献
Surface properties of foam films formed from aqueous dispersions of dipalmitoyl-phosphatidylcholine (DPPC) and from solutions of a phospholipid fraction of lung surfactant (TPL) are studied employing the foam film method. Experiments are carried out within a wide range of NaCl concentrations (Cel) and the ranges of Cel determining formation of common films (CF), common black films (CBF) and bilayer Newton black films (NBF) are found. The thickness (h) of the CF and CBF decreases with the increase of Cel until the critical electrolyte concentrations (Cel, cr) is reached. The determined Cel, cr that characterize the transition to NBF show that Cel, cr of the TPL films is an order of magnitude higher than that of the DPPC films. The measured h of the TPL films is higher than that of the DPPC films in the whole Cel range. Besides, only the h(Cel) curve of the DPPC films outlines a metastable Cel range where both CF and NBF are obtained. Both the h(Cel) curves and the direct measurements of the disjoining pressure isotherms of the DPPC films (Π(h) isotherms) demonstrate the role of electrostatic repulsive forces for the stability of the phospholipid films The obtained results are compared with the DLVO theory equations and the evaluated potentials of the diffuse electric layer φ0 20 mV for the DPPC films and φ0 100 mV for TPL films show the strong effect of the charged phospholipids in the TPL mixture on the electric properties at the film interfaces. 相似文献
In pulmonary tuberculosis, Mycobacterium tuberculosis bacteria reside in the alveoli and are in close proximity with the alveolar surfactant. Mycolic acid in its free form and as cord factor, constitute the major lipids of the mycobacterial cell wall. They can detach from the bacteria easily and are known to be moderately surface active. We hypothesize that these surface-active mycobacterial cell wall lipids could interact with the pulmonary surfactant and result in lung surfactant dysfunction. In this study, the major phospholipid of the lung surfactant, dipalmitoylphosphatidylcholine (DPPC) and binary mixtures of DPPC:phosphatidylglycerol (PG) in 9:1 and 7:3 ratios were modelled as lung surfactant monolayers and the inhibitory potential of mycolic acid and cord factor on the surface activity of DPPC and DPPC:PG mixtures was evaluated using Langmuir monolayers. The mycobacterial lipids caused common profile changes in all the isotherms: increase in minimum surface tension, compressibility and percentage area change required for change in surface tension from 30 to 10 mN/m. Higher minimum surface tension values were achieved in the presence of mycolic acid (18.2 ± 0.7 mN/m) and cord factor (13.28 ± 1.2 mN/m) as compared to 0 mN/m, achieved by pure DPPC film. Similarly higher values of compressibility (0.375 ± 0.005 m/mN for mycolic acid:DPPC and 0.197 ± 0.003 m/mN for cord factor:DPPC monolayers) were obtained in presence of mycolic acid and cord factor. Thus, mycolic acid and cord factor were said to be inhibitory towards lung surfactant phospholipids. Higher surface tension and compressibility values in presence of tubercular lipids are suggestive of an unstable and fluid surfactant film, which will fail to achieve low surface tensions and can contribute to alveolar collapse in patients suffering from pulmonary tuberculosis. In conclusion a biophysical inhibition of lung surfactant may play a role in the pathogenesis of tuberculosis and may serve as a target for the development of new drug loaded surfactants for this condition. 相似文献
Depending on their hydrophobicity, peptides can interact differently with lipid membranes inducing dramatic modifications into their host systems. In the present paper, the interaction of a synthetic peptide with a scrambled hydrophobic/hydrophilic sequence (Pro-Asp-Ala-Asp-Ala-His-Ala-His-Ala-His-Ala-Ala-Ala-His-Gly) (PADH) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) model membranes has been investigated by differential scanning calorimetry (DSC), adopting three different experimental approaches. In the first, the peptide is forced to be included into the hydrocarbon region of the lipid bilayer, by codissolving it with the lipid giving rise to mixed multilamellar vesicles–peptide systems; in the second, this system is passed through an extruder, thus producing large unilamellar vesicles–peptide systems; in the third, it is allowed to interact with the external surface of the membrane.
The whole of the DSC results obtained have shown that the incorporation of the peptide into the lipid bilayer by means of the first method induces a decrease in the enthalpy of the gel–liquid crystal transition of the membrane and a shift of the transition to the lower temperatures, thus resembling, in spite of its prevalently hydrophilic nature, the behavior of transbilayer hydrophobic peptides. The extrusion of these systems creates unilamellar vesicles free of peptides but of smaller size as evidenced by the decreased cooperativity of the transition. The peptide, added externally to the DPPC model membrane, has no effect on the phase behavior of the bilayer.
These findings suggest that the effect of the interaction of scrambled hydrophobic/hydrophilic peptides into lipid bilayers strongly affects the thermotropic behavior of the host membrane depending on the preparation method of the lipid/peptide systems. The whole of the results obtained in the present paper can be useful in approaching studies of bioactive peptides/lipids systems. 相似文献