Low Critical Micellar Concentration Research Articles

Use of a Mixture of n-Dodecyl-β-d-maltoside and Sodium Dodecyl Sulfate in Poly(dimethylsiloxane) Microchips To Suppress Adhesion and Promote Separation of Proteins

Dynamic modification of poly(dimethylsiloxane) channels using a mixture of n-dodecyl-beta-D-maltoside (DDM) and sodium dodecyl sulfate (SDS) is able to suppress analyte adsorption and control electroosmotic flow (EOF). In this mixed surfactant system, the nonionic surfactant DDM functions as a surface blocking reagent, whereas the anionic surfactant SDS introduces negative charges to the channel walls. Changing the DDM/SDS mixing ratio tunes the surface charge density and the strength of EOF. Using 0.1% (w/v) DDM and 0.03% (w/v) SDS, Alexa Fluor 647 labeled streptavidin can be analyzed according to the charges added by the fluorophores. Protein molecules with different numbers of fluorophores are well resolved. DDM and SDS also form negatively charged mixed micelles, which act as a separation medium. The low critical micellar concentration of DDM/SDS mixed micelles also allows the use of SDS at a nondenaturing concentration, which enables the analysis of proteins in their native state. The immunocomplex between a membrane protein, beta2 adrenergic receptor, and anti-FLAG antibody has been fully separated using 0.1% (w/v) DDM and 0.03% (w/v) SDS. We have also analyzed the composition of light-harvesting protein-chromophore complexes in cyanobacteria.

Synthesis and characterization of well‐defined, amphiphilic poly(N‐isopropylacrylamide)‐ b‐[2‐hydroxyethyl methacrylate‐poly(ϵ‐caprolactone)]n graft copolymers by RAFT polymerization and macromonomer method

AbstractThe well‐defined, thermosensitive and biodegradable graft copolymers, poly(N‐isopropylacrylamide)‐b‐[2‐hydroxyethyl methacrylate‐poly(ε‐caprolactone)]n (PNIPAAm‐b‐(HEMA‐PCL)n) (n = 3 or 9), were synthesized by combining reversible addition‐fragmentation chain transfer polymerization and macromonomer method. The copolymers were able to self‐assemble into micelles in water with low critical micellar concentration and demonstrated temperature sensitivity with a lower critical solution temperature at around 36 °C. Transmission electron microscopy shows that the micelles exhibit a nanosized spherical morphology within a size range of 30–100 nm. The PNIPAAm‐b‐(HEMA‐PCL)3 copolymer exhibited biodegradation and low cytotoxicity. The paclitaxel‐loaded PNIPAAm‐b‐(HEMA‐PCL)3 micelles displayed thermosensitive controlled release behavior, which indicates potential as drug carriers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5354–5364, 2007

First Chemical Synthesis, Aggregation Behavior and Cholesterol Solubilization Properties of Pythocholic Acid and 16α‐Hydroxycholic Acid

AbstractThe first chemical synthesis of pythocholic acid, a major component of python's bile, and 3α,7α,12α,16α‐tetrahydroxy‐5β‐cholan‐24‐oic acid (16α‐hydroxycholic acid), a minor component in Shoebill stork's bile, was achieved starting from readily available cholic acid in overall yields of 5 % and 5.5 %, respectively, through a common intermediate. A biomimetic template‐directed remote functionalization strategy was utilized to selectively functionalize C‐16 of the steroid skeleton. This synthesis involves a series of regio and chemoselective transformations. Pythocholic acid showed unusually low critical micellar concentration (CMC) with high cholesterol solubilization ability. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Surface-active properties of the antitumour ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine)

The surface activity and interaction with lipid monolayers and bilayers of the antitumour ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine) have been studied. Edelfosine is a surface-active soluble amphiphile, with critical micellar concentrations at 3.5 μM and 19 μM in water. When the air–water interface is occupied by a phospholipid, edelfosine becomes inserted in the phospholipid monolayer, increasing surface pressure. This increase is dose-dependent, and reaches a plateau at ca. 2 μM edelfosine bulk concentration. The ether lipid can become inserted in phospholipid monolayers with initial surface pressures of up to 33 mN/m, which ensures its capacity to become inserted into cell membranes. Upon interaction with phospholipid vesicles, edelfosine exhibits a weak detergent activity, causing release of vesicle contents to a low extent (<5%), and a small proportion of lipid solubilization. The weak detergent properties of edelfosine can be related to its very low critical micellar concentrations. Its high affinity for lipid monolayers combined with low lytic properties support the use of edelfosine as a clinical drug. The surface-active properties of edelfosine are similar to those of other “single-chain” lipids, e.g. lysophosphatidylcholine, palmitoylcarnitine, or N-acetylsphingosine.

Synthesis and characterization of RGD-fatty acid amphiphilic micelles as targeted delivery carriers for anticancer agents

Novel amphiphilic conjugates consisting of an Arg-Gly-Asp (RGD) peptide binding motif and aliphatic fatty acids of varying chain length (C10–C18) were synthesized and evaluated for their ability to form micelles and bind specifically to αVβ3 integrin over-expressing tumor cells. The aphilphiles were characterized by IR, proton NMR and mass spectrometry. The size and zeta potential of the resultant micelles were ranged from 178 to 450 nm and − 13.5 to 39.6 mV, respectively. The critical micellar concentration (CMC), drug loading efficiency and tumor cell binding of these amphiphiles were determined. The CMC values, determined by pyrene fluorescent probe method, ranged from 0.02 to 0.12 mM for C14-RGD, C16-RGD and C18-RGD. The C18-RGD micelles with lowest CMC were found to increase the solubility of taxol, a model anticancer drug, by 87%. C18-RGD amphiphiles also exhibited significantly higher (12.1 ± 1.14%, P < 0.05) binding to αVβ3 integrin over-expressing human breast cancer cells (HTB-129) when compared to normal human epidermal keratinocyte (NHEK) cells (6.68 ± 0.34). The results from this study demonstrated the feasibility of designing RGD-fatty acid amphiphiles as micellar drug delivery carriers to target to cancer cells.

Benzyl β-malolactonate: synthesis, copolymerization and design of novel biodegradable macromolecular surfactants

Racemic [R,S] benzyl β-malolactonate monomer (MLABz) was synthesized according to the well-established “aspartic acid” route and purified to such an extend that it allowed the controlled synthesis of poly([R,S] β-malic acid)-b-poly((D,L)-lactide) diblock copolymers by a versatile three-step pathway combining anionic and coordination-insertion ROP of MLABz and lactide monomers, respectively. For the sake of comparison, amphiphilic poly([R,S] β-malic acid)-b-poly(e-caprolactone) diblock copolymers of identical composition were synthesized as well. The associating behavior of monodisperse diblock copolymers consisting of water-soluble poly(β-malic acid) block and hydrophobic polylactide or poly(e-caprolactone) block was studied in aqueous solution. Accordingly, both types of copolymers were dissolved directly in water and (dynamic) surface tension measurements were carried out. It came out that poly(β-malic acid)-bpoly((D,L)-lactide) amphiphilic diblock copolymers showed tensioactive properties with a lower critical micellar concentration, a higher efficiency of adsorption and a better monomer coefficient diffusion compared to corresponding poly(β-malic acid)-b-poly(e-caprolactone) diblock copolymers of comparative composition.

Equilibrium and Dynamic Surface Tension Properties of Aqueous Solutions of Sulfonated Cationic‐Nonionic Fluorocarbon Surfactants

The equilibrium and dynamic surface tension properties in aqueous solutions of nonionic and cationic fluorinated surfactants bearing a sulfonated group are reported. Both surfactants show low critical micellar concentration and very low equilibrium surface tension values, but the cationic surfactant is more effective at decreasing surface tension, which is attributed to a small surface area per molecule. In dynamic surface tension measurements both surfactants show an induction time, which is longer for the nonionic surfactant with a higher molecular weight, slower diffusion rates, and higher molecular surface area. The dynamic behavior of surface tension is modeled by a series of exponentials from which a relaxation time for surface tension decay can be estimated. This relaxation time is faster for the cationic surfactant and decreases with both surfactant concentration and temperature. In mixtures of both surfactants, the values of the relaxation time are between those of the pure surfactants, indicating neither synergism nor antagonism.

Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs

To develop self-assembling systems increasing the solubility of poorly water-soluble drugs. Low molecular weight liquid biodegradable copolymers were synthesized by ring-opening polymerization using caprolactone (CAP) and trimethylenecarbonate (TMC) as monomers. Various initiators were evaluated. The emulsifying and self-assembling properties were investigated by a water titration method. The self-assembling systems were characterized for size, shape, isotropic behavior, cloud point, surface charge, and critical micellar concentration in order to optimize the polymer synthesis. Finally, the improvement of solubility of model drugs was assessed. Only diblock monomethyl ether PEG-CAP/TMC copolymers synthesized with monomethyl ether polyethyleneglycol 550 to 2000 as initiator have shown self-assembling properties: upon dilution, these copolymers formed an isotropically clear solution with droplet sizes in the range of 20 to 100 nm. The hypothesis that these diblock polymers form micelles was confirmed by their low critical micellar concentration (10(-5) g/ml). The copolymers initated with mmePEG750 had a higher cloud point and better colloidal stability than those initiated with mmePEG 550. The solubility of the poorly water-soluble drugs was increased by 1 to 2 orders of magnitude. Good reproducibility was observed from batch to batch. The polyester diblock copolymer mmePEG750-CAP/TMC forms spontaneously stable micelles in aqueous medium and increases the solubility of lipophilic drugs. They are very promising vehicles for the oral delivery of poorly water-soluble drugs.

Structural changes in CTAB/H2O mixtures using a rheological approach

A complete, rheometrical analysis (steady, oscillatory and transient stress-relaxation experiments) may be performed to indirectly elucidate the inner structure of surfactant solutions over a wide range of physicochemical conditions. In this paper, structure and structural changes in cetyltrimethylammonium bromide (CTAB)/H2O mixtures have been studied by a set of rheological experiments as a function of composition (2–40 wt% CTAB) and temperature (20–70 °C). This system was chosen for several reasons: firstly, it forms elongated micelles and exhibits a strong viscoelasticity at low concentrations (ca. 2 wt%); secondly, it has a low critical micellar concentration and a Krafft temperature close to the room temperature; third, a nematic phase (type-I, N) is formed in the concentration range 25–29 wt% with a clearing temperature of ca. 40 °C. The nematic phase is intermediate to a micellar isotropic phase (L1), at low concentration, and to a normal hexagonal lyomesophase (H1) at high concentration of CTAB. The L1 phase, consisting of a very large region, exhibited different rheological properties. At 30 °C, viscoelastic data revealed a sphere-to-cylinder transition in shape of micelles in mixtures above 14 wt% CTAB. By increasing further the composition, a fast micellar growth was observed without reaching an entangled phase. The evolution of micellar morphology was also recorded with increasing temperature. The nematic and hexagonal phases, made by similar structural units (i.e. unconnected cylindrical aggregates), behaved like shear thinning materials and showed a comparable viscoelastic spectrum consisting of fast and slow relaxation processes. The slower relaxation times were interpreted as a relaxation of a shear-induced orientation that involved large lyotropic domains. Faster relaxation times (<1 s), on the contrary, could be related to dynamics or kinetics of stiff cylindrical aggregates.

Adsorption and Interfacial Properties of the Cationic Gemini Surfactant of Ethanediyl-α,β-Bis(Cetyldimethylammonium Bromide)

The cationic gemini surfactant ethanediyl-α,β-bis(cetyldimethylammonium bromide (16-2-16) was synthesized and characterized. Aggregation of the surfactant molecules was established by surface tension measurements and viscosity methods. Some thermodynamic parameters, such as the adsorption capacity of the surface, the molecular area associated with adsorption and the free energy of micellization, were calculated from plots of the surface tension versus the concentration. The dynamic surface and interfacial tensions were measured using the pendant drop method at the air/water surface and the dodecane/water interface. The experimental curve was close to the orientation and interaction models of the surface equations of state. In comparison to conventional cationic surfactants, 16-2-16 has a very low critical micellar concentration (cmc), a higher level of surface adsorption and a lower adsorption molecular area. Due to its unique molecular structure and size, 16-2-16 adsorbs at surfaces and interfaces, but r...

Molecular characterization of α,β-poly( N-2-hydroxyethyl)- dl-aspartamide derivatives as potential self-assembling copolymers forming polymeric micelles

A family of graft copolymers derivatives obtained from α,β-poly( N-2-hydroxyethyl)- dl-aspartamide (PHEA) have been studied as potential self-assembling macromolecules forming stable polymeric micelles at low critical micellar concentration. These polymers are obtained grafting on PHEA poly(ethylene glycol) (PEG) ( M w 5000 g/mol) (PHEA–PEG), hexadecylamine (PHEA–C 16) or both moieties (PHEA–PEG–C 16). The PHEA derivatives were characterised by a multi-angle light scattering (MALS) photometer on line to a size exclusion chromatography system in obtaining the molar mass distribution of the polymers. In addition, to investigate the capacity to form micellar aggregates in aqueous medium the MALS photometer was used in off-line batch mode in obtaining molar mass and dimension of the polymeric aggregates.

Micellar Formation Study of Crown Ether Surfactants

AbstractFluorescence probe and nuclear magnetic resonance (NMR) methods were employed to investigate the micellation of prepared crown ether surfactants, e.g. decyl 15‐crown‐5 and decyl 18‐crown‐6. Pyrene was employed as the fluorescence probe to evaluate the critical micellar concentration (CMC) of these surfactants in aqueous solutions while spin lattice relaxation times (T1) and chemical shifts of H‐1 NMR were applied in non‐aqueous solutions. Decyl 15‐crown‐5 with lower CMC forms micelles much easier than decyl 18‐crown‐6 with higher CMC in aqueous solutions, whereas decyl 18‐crown‐6 forms micelles easier than decyl 15‐crown‐5 in nonaqueous solutions. Comparison of the CMC of crown ether surfactants and other polyoxyethylene surfactants such as decylhexaethylene glycol was made. Effects of salts and solvents on the micellar formation were also investigated. In general, additions of both alkali metal salts and polar organic solvents into the aqueous surfactant solutions increased in the CMC of these surfactants. The formation of micelles in organic solvents such as methanol and acetonitrile was successfully observed by the NMR method while it was difficult to study these surfactants in organic solutions by the pyrene fluorescence probe method. The NMR study revealed that the formation of micelles resulted in the decrease in all H‐1 spin lattice relaxation times (T1) of hydrophobic groups, e.g. CH3 and CH2, and hydrophilic group OCH2 of these surfactants. However, upon the micellar formation, the H‐1 chemical shifts (δ) of these surfactant hydrophobic groups were found to shift to downfield (increased δ) while the chemical shift of the hydrophilic group OCH2 moved to up‐field. Comparison of the spin lattice relaxation time and H‐1 chemical shift methods was also made and discussed.

Uptake and metabolism of exogenous glycosphingolipids by cultured cells

Exogenous glycosphingolipids, especially gangliosides, are used to study transport and metabolism of their endogenous counterparts as well as their role in cell adhesion, cell recognition and signal transduction. Unlike monodispersed solutes, in aqueous media ganglioside molecules aggregate into micelles (or bilayer structures) with a very low critical micellar concentration. Upon addition to cells in culture, exogenous gangliosides bind to the cell surface in three operationally defined modes: loosely associated micelles removable by serum; tightly attached micelles removable by proteases such as trypsin; and ganglioside molecules inserted into the outer leaflet of the plasma membrane. As shown by a biotin-labeled derivative of the ganglioside GM1 these inserted molecules are endocytosed and transported to intralysosomal membranes for catabolism. The benefit from using (partially) nondegradable as well as semi-truncated glycosphingolipids in transport studies is discussed.

Distillery and curd whey wastes as viable alternative sources for biosurfactant production

Biosurfactant production from synthetic medium and industrial waste, viz. distillery and whey wastes was investigated by using an oily sludge isolate Pseudomonas aeruginosa strain BS2. In synthetic medium separately supplemented with glucose and hexadecane as water-soluble and -insoluble carbon sources, respectively, strain BS2 reduced the surface tension of the fermentation broth from 57 to 27 mN/m. The culture produced biosurfactant during the stationary growth phase and its yield was 0.97 g/l. The culture utilized distillery and whey wastes for its growth, as maximum cell counts reached to 54 × 108 and 64 × 109 c.f.u./ml from an initial inoculum size of 1 × 05 c.f.u./ml, respectively, within 48 h of incubation and in these wastes the yields of biosurfactant obtained were 0.91 and 0.92 g/l, respectively. In synthetic medium, distillery and whey wastes, strain BS2 produced a crystalline biosurfactant which belonged to the category of secondary metabolites and its maximum production occurred after the onset of nitrogen-limiting conditions. After recovering biosurfactant from the fermented waste, the chemical oxygen demand (COD) of distillery and whey wastes was significantly reduced by 81 and 87%, respectively. Total acids, nitrogen and phosphate levels in distillery waste were reduced by 90, 92 and 92%, respectively, while in case of whey waste the concentration of these nutrients was reduced by 88, 95 and 93%, respectively. The isolated biosurfactant possessed potent surface active properties, as it effectively reduced the surface tension of water from 72 to 27 mN/m and formed 100% stable emulsions of a variety of water-insoluble compounds such as hydrocarbons, viz. hexadecane, crude oil, kerosene and oily sludge and pesticides, viz. dichlorodiphenyltrichloroethane (DDT) and benzene hexachloride (BHC). The effectiveness of biosurfactant was also evident from its low critical micellar concentration (CMC) which was 0.028 mg/ml.

Design of functional polymeric micelles as site-specific drug vehicles based on poly ( α-hydroxy ethylene oxide-co- β-benzyl l-aspartate) block copolymers

Poly ( α-hydroxy ethylene oxide-co- β-benzyl l-aspartate), α-hydroxy PEO/PBLA, block copolymers were used for the formulation of new functional polymeric micelles. They have a small diameter (about 30 nm) and a very low critical micellar concentration (cmc) in water, ca. 4 mg l −1. Doxorubicin (DOX) was physically entrapped into the hydrophobic inner core of these functional micelles. The diameter of DOX-loaded α-hydroxy PEO/PBLA micelles was determined to be approximatively the same as the diameter of the corresponding empty micelles, ca. 25 nm. Moreover, the DOX-loaded functional micelles, as the corresponding empty micelles, were shown to be stable in 0.1 M phosphate buffered solution (PBS) pH 7.4 even in presence of proteins. The cytotoxicity of DOX-loaded functional micelles against P388D1 leukemia cells was studied and compared to the one of DOX-loaded α-methoxy PEO/PBLA micelles and to the cytotoxicity of both α-hydroxy and α-methoxy PEO/PBLA micelles. From this study it was concluded that the DOX-loaded functional micelles seem to have a slightly higher cytotoxicity than the DOX-loaded α-methoxy PEO/PBLA micelles, while both empty micelles were shown to be non-cytotoxic against P388D1 leukemia cells.

Trypsin secretion in Musca domestica larval midguts : A biochemical and immunocytochemical study

Musca domestica larvae have trypsin in their midgut cells and contents, mainly at the posterior region. Both soluble and membrane-bound forms of trypsin are found. Membrane-bound trypsin is not affected by papain or phosphatidylinositol-specific phospholipase C, although it is solubilized with equal efficiency by detergents with high and low critical micellar concentrations. The solubilization increases at high pH values in the presence or absence of detergent. Once solubilized, membrane-bound trypsin behaves as a hydrophilic protein. M. domestica trypsin was purified to homogeneity and used to raise antibodies in a rabbit. A Western blot of M. domestica membrane-bound and soluble midgut proteins, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis using trypsin antiserum, showed only bands co-migrating with trypsin. With this antiserum, trypsin was immunolocalized in the membranes of secretory and Golgi vesicles, surface of microvilli and midgut contents of M. domestica posterior midgut. The data suggest that trypsin is bound to the secretory vesicle membrane by a hydrophobic peptide anchor. Upon exocytosis, most trypsin is solubilized apparently because the neutral pH of the luminal contents causes a conformational change which hinders part of the trypsin anchor.

Extracti-Gel TM D chromatography is a simple, efficient method for removing digitonin during receptor purification: application to the kl opioid receptor

Digitonin is widely used for extracting active neurotransmitter receptors from membranes. However, its low critical micellar concentration has made its removal from samples problematic. Here we report that digitonin can be efficiently removed (> 90%) from solution using Extracti-Gel TM D, a detergent-absorbing matrix. Active K l opioid receptors solubilized from brain survive Extracti-Gel TM D chromatography with a recovery of 50–55% and 25% dilution by added volume. The loss of receptor and the dilution, however, are compensated for to a large extent by the disinhibition of binding that results from the removal of digitonin. Extracti-Gel TM D chromatography had little or no effect on the apparent equilibrium dissociation constant for [ 3H]U-69,593 binding to the K l receptor. We conclude that Extracti-Gel TM D column chromatography is a simple, highly efficient and practical method for markedly reducing the concentration of digitonin in biological samples. Application of the procedure should allow characterization of digitonin-solubilized receptors with minimal complications from bound digitonin and extend the usefulness of digitonin to studies going beyond the initial stages of receptor purification.

α, ω‐Dipolar amphiphiles: Influence of rigid and flexible units on aggregation behavior

AbstractMono‐ and α,ω‐dipolar amphiphiles with hydrophilic pyridinium head groups, and flexible and rigid hydrophobic parts have been synthesized. Surface tension and conductivity measurements proved that micellar aggregates for amphiphiles 1–4 are formed. The incorporation of rigid units leads to a decrease in the critical micellar concentration (CMC): the rigid monopolar amphiphile 2 aggregates at lower concentration than the flexible monopolar amphiphile 1. A similar decrease was observed when chain ends were connected: the flexible α,ω‐dipolar amphiphile 3 has a lower CMC than the flexible monopolar amphiphile 1. The more flexible amphiphiles 1–3 allow the formation of micelles of different shape leading to both CMC and Ct values. For the α,ω‐dipolar amphiphile 4 with a rigid azoxybiphenylene core, the possibility of different micellar shapes is reduced, leading only to a CMC value (CMC = Ct). For the flexible α,ω‐dipolar amphiphile 3, only a small, but linear viscosity increase with concentration is found. Very viscous solutions were measured for the rigid α,ω‐dipolar amphiphile 4 above a certain concentration. Phase diagrams of amphiphiles 3 and 4 were determined using polarization‐microscopy and X‐ray measurements. Flexible α,ω‐dipolar amphiphile 3 shows a lyotropic mesophase only at very high concentration (83 mass %). In contrast, rigid analog 4 forms stable lyotropic mesophases at 16 mass %. Both nematic and higher ordered mesophases (probably lamellar) are found for the rigid α,ω‐dipolar amphiphile 4.

Cholestasis, metabolism and biliary lipid secretion during perfusion of rat liver with different bile salts

The biological effects of bile acids depend largely upon their molecular structure. When bile acid uptake exceeds the maximal biliary secretory rate (SRm) cholestasis occurs. In order to characterize the influence of bile acid structure on its cholestatic potency we systematically studied SRm, maximal bile flow, maximal and cumulative phospholipid and cholesterol secretion with different taurine-conjugated tri-, di- and keto bile acids (Table I) in the isolated perfused rat liver. Bile acids with a high critical micellar concentration (CMC) promoted the greatest bile flow; a positive non-linear correlation between CMC and maximal bile flow was found. 3α-Hydroxylated bile acids with a hydroxyl group in 6α and/or 7β position and lacking a 12α hydroxy group had a high SRm. SRm was not related to CMC or maximal bile flow, respectively. Phospholipids and cholesterol were secreted in a nearly fixed ratio of 12:1; a strong linear relationship could be observed. Cumulative phospholipid secretion over 48 min was significantly lower for non and poor micelle forming bile acids (TDHC and TUC) than for those with comparatively low CMC values (TUDC, TC, THC, THDC, TCDC) (70–140 vs. 210–450 nmol/g liver). At SRm all bile acids with good micelle forming properties showed a similar cumulative biliary lipid output. However, when biliary lipid output was related to 1 μmol bile acid secreted bile acids with a low SRm induced the highest lipid secretion (TCDC, TC). These data (1) demonstrate that a 6α and/or a 7β hydroxy group on the steroid nucleus reduce cholestatic potency if the 12α hydroxy group is absent, (2) suggest that in the case of micelle forming bile acids the total amount of phospholipids secreted in bile (depletion of cellular phospholipids) is associated with the occurrence of cholestasis whereby bile acids with a low SRm deplete the cellular phospholipid content at much lower bile acid concentrations than those with a higher SRm and (3) imply that bile acids with non and poor micelle forming properties (TDHC, TUC) presumably do not cause cholestasis (solely) by depletion of cellular phospholipids.

Membrane lipid phase behaviour and lipid-protein interactions

One of the most distinguishing features of nearly all biological membranes is that they contain a highly complex assortment of polar lipids. Only a few major lipid classes can be recognized but there is a whole spectrum of molecular species within each of these major lipid classes which differ in the type, length, and number of unsaturated residues of their hydrophobic component. There is a general consensus, based on observations that have been obtained by a variety of biophysical methods, that the lipid constituents of all biological membranes are arranged in a bilayer configuration in which the polar groups are located on the outside, in contact with the aqueous medium, and the hydrocarbon substituents are oriented toward the interior to form a hydrophobic domain that excludes water. It has been argued on the basis of the hydrophilic to hydrophobic balance within the molecules that membrane lipids have a relatively low critical micellar concentration and a discrete distribution of domains within the molecule and this is responsible for creating a stable bilayer structure.