Lipid-surfactant mixtures

Lipid-surfactant mixtures have gained much interest in context with the solubilization of membranes and with the problem of reconstituting membrane proteins into artificial membrane systems such as unilamellar vesicles. For the solubilization of membranes, a sufficiently high concentration of an aqueous micellar solution has to be added to the membrane suspension, so that the bilayers are transformed into mixed micelles containing surfactant, membrane lipids, and membrane proteins. This solubilization process is quite complicated and the necessary amounts of surfactant for complete solubilization depends on the nature of the surfactant, the type of membrane, and the total concentration of lipid and surfactant. 

For a better understanding of this process, experiments with model membrane systems have been undertaken and an overall picture has emerged for the low concentration regime of lipid and surfactant, which can be described as follows. 

Addition of surfactant molecules to lipid vesicles first leads to a partitioning of the surfactant into the lipid bilayers, an equilibrium is established, the partition coefficient depending on the nature of the lipids in the membrane and the chemical stmcture of the surfactant. Further increase of the total surfactant concentration leads finally to a saturation of the bilayers with surfactant molecules and first mixed micelles of a different surfactant to lipid ratio appear. Over a certain concentration range mixed bilayers and mixed micelles coexist until finally all bilayers have been transformed into micelles. 

This process ean be easily followed by titration calorimetry, as described below. In particular, the partition coefficients and the boundaries of the coexistence region can be determined. In addition, the thermodynamic quantities obtained from these calorimetric experiments provide new insight into the molecular interactions in these systems. 

In principle, the partition coefficient can be calculated from this decrease in 7ni [108], However, ITC experiments and also experiments using fluorescent probes have shown that the partition coefficient is a function of OG concentration in the bilayer, decreasing with increasing surfactant saturation of the bilayer. The approach using DSC curves therefore leads to incorrect results. A further increase of the OG concentration to values where partial or complete micellization for liquid-crystalline bilayers is observed, still leads to DSC curves with a clear endo-thennic peak, which is now almost independent of total OG concentration. Obviously, the mixed micelles fonned at higher temperatures convert to bilayer phases upon cooling and the phase behavior at lower temperature is more complicated. 

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The most common methods for preparing liposomes32, which are not discussed here in detail, are the ultrasonication of lipid suspensions in water 6), the injection of alcoholic or etheral solutions of lipid into water, the dialysis of lipid-surfactant mixtures, and the removal of lipid films on glass surfaces by simple hand-shaking in water. 

Y Roth, E Opatowski, D Lichtenberg, MM Kozlov. Phase behavior of dilute aqueous solutions of lipid-surfactant mixtures Effects of finite size of micelles. Langmuir In press. (1999). 

DSC studies of lipid-surfactant mixtures in the regime of low surfactant concentrations provide some insight into the partition coefficient of the surfactant molecule between water and the bilayer. We have systematically studied the be-havior of DMPC/octylglucoside (DMPC/OG) mixtures by ITC and DSC. The results of the ITC experiments will be described below. Figure 31 shows as an example some DSC curves of DPPC/OG mixtures as a function of total OG concentration. First, a decrease of the transition temperature due to preferential OG partitioning into the L,t-phase bilayers is observed. 

Proteins SP-B and SP-C are small extremely hydrophobic polypeptides consisting of 79 and 35 amino acid residues, respectively." 0 Aliphatic branched amino acids constitute 23 of the 35 residues of the C-terminal part of protein C, which is also palmitoylated on two cysteine residues. SP-B is formed from a large 381-residue precursor. The mature protein contains seven cysteines and disulfide bridges. Both proteins have major effects on the properties of the surfactant mixture. They promote rapid reorganization of lipid layers, an important consideration for the functioning of the surfactant. Infants lacking SP-B suffer severe respiratory failure with high mortality.6... 

The biochemical work described in Chapter 5 indicated that the microbubble surfactant mixture actually represents a glycopeptide-lipid-oligosaccharide complex, which is reversibly held together by both hydrogen bonding and nonpolar interactions. The experiments described below were undertaken to examine in detail the surface properties of the microbubble surfactant complex at the air/water interface (ref. 361). 

Fig. 7.1 shows a typical H-NMR spectrum obtained with the partially purified, microbubble surfactant mixture prior to monolayer formation. For comparison, Table 7.1 gives the chemical-shift data for the proton resonances that can be readily identified in the 1 H-NMR spectra of long-chain acyl lipids (ref. 395-401). 

The action of lipid-protein mixtures, mimicking those of physiological lung surfactants can be, and has been, studied in Langmuir troughs. For instance, in one of such studies the monolayers were subjected to compression-expansion cycles. At... 

The mesophase behaviour of surfactant- and lipid-water mixtures... 

Photon Correlation Spectroscopy Diameters of Dynasan 114, 116, and 118 Solid Lipid Nanoparticles Stabilized with Mixtures of Cholic Acid Sodium Salt (NaCh) and poloxamer 407 (5% Lipid, 0.5% Surfactant) to Assess the Influence of Different Surfactant Mixtures on the Enzymatic Degradation (Lipase/Colipase Assay) of Solid Lipid Nanoparticles... 

The lung alveolar surfactant (AS) is a complex lipid-protein mixture, essential for the normal respiratory activity [1-4]. The main AS function in vivo is to reduce the alveolar surface tension (y, mN/m) and to provide alveolar stability [5,6], The absence of a mature AS in the lungs is the main reasmi for the development of neonatal respiratory distress syndrome (NRDS) that often has a lethal outcome [7]. 

Baglioni P —> Carretti E Baptista ALF, Coutinho PJG, Real Oliveira MECD, Rocha Gomes JIN Lipid interaction with textile fibres in dyeing conditions 88 Barbosa EFG —> Santos MSCS Bechinger C —> Brunner M Behr J-P Lleres D Bergstrom M, Eriksson JC Synergistic effects in binary surfactant mixtures 16... 

In this chapter, studies involving surfactants are somewhat arbitrarily separated from those that concern lipids. Similarities or differences of behavior are pointed out whenever necessary. The chapter is organized as follows. Section II reviews the dynamics of the surfactant Lg phase and of transitions between various lyotropic phases. Section III deals with the dynamics of phase transitions in lipid/water mixtures. Section IV reviews the dynamics of phase transitions induced by shear. Section V concludes this chapter. 

Surfactant is a lipid-protein complex that is synthesized and released hy alveolar type II epithelial cells. This complex surface-active compound contains both hydrophobic and hydrophilic regions to allow the molecule to spontaneously adsorb to and form monolayers along the air-liquid interface. The role of surfactant in pulmonary fluid mechanics depends on its natural ability to disrupt intermolecular forces by interfering with the attractive forces between water molecules at the interfacial surface—thus lowering the surface tension. While this surfactant mixture is largely comprised of lipids (90%), the surfactant proteins (10%) are required for normal function (Hall et al. 1992 Yu and Possmayer 1993). Finally, the molecule dipalmitoyl phosphatidylcholine (DPPC) makes up 80% of the phospholipid and is largely responsible for the ultra-low surface tensions necessary for respiratory function (<5 dyn/cm) (Klaus et al. 1961 Hawco et al. 1981 Tchoreloff et al. 1991). 

SEDDS are isotropic mixtures of lipid, surfactant, cosurfactant and, sometimes, cosolvents, and drug substance that can spontaneously form fine oil-in-water microemulsions under mild agitation following dilution with an aqueous phase (Neslihan Gursoy... 

Systematic studies of the phase behavior of lipid-surfactant systems have been performed particularly on mixtures of surfactants of the Ci2EOn type and phosphatidylcholines with different chain lengths and saturation [109-113]. The phase diagrams of these pseudo-binary mixtures in excess water are complicated and become even more so when the water content is varied. 

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

FIG. 1 Self-assembled structures in amphiphilic systems micellar structures (a) and (b) exist in aqueous solution as well as in ternary oil/water/amphiphile mixtures. In the latter case, they are swollen by the oil on the hydrophobic (tail) side. Monolayers (c) separate water from oil domains in ternary systems. Lipids in water tend to form bilayers (d) rather than micelles, since their hydrophobic block (two chains) is so compact and bulky, compared to the head group, that they cannot easily pack into a sphere [4]. At small concentrations, bilayers often close up to form vesicles (e). Some surfactants also form cyhndrical (wormlike) micelles (not shown). 

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