Effects of sterols on permeability and phase transitions of bilayers from phosphatidylcholines lacking acyl groups

Bittman, Robert; Clejan, Sanda; Jain, Mahendra Kumar; Deroo, Paul W.; Rosenthal, Arthur

doi:10.1021/bi00513a013

Cited by 67 publications

(25 citation statements)

References 35 publications

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“…The reduction of the leak conductance of asolectin membranes induced by cholesterol is consistent with findings that cholesterol greatly reduces the permeability of lipid membranes to different substances (19)(20)(21)(22), which is generally attributed to the ability of cholesterol to promote order in lipid chains. However, we observed that cholesterol incorporation into asolectin membranes essentially eliminated the PA-induced increase in proton selectivity observed in pure asolectin membranes.…”

Section: Membranes Modified By Fa In the Bathsupporting

confidence: 88%

Fatty acid flip-flop and proton transport determined by short-circuit current in planar bilayers

Brunaldi

Arcísio-Miranda

Abdulkader

et al. 2005

Journal of Lipid Research

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The effect of palmitic acid (PA) and oleic acid (OA) on electrical parameters of planar membranes was studied. We found a substantial difference between the effects of PA and OA on proton transfer. PA induced a small increase in conductance, requiring a new technique for estimating proton-mediated currents across low-conductance planar bilayers in which an electrometer is used to measure the transmembrane current under virtual short circuit (SCC). Open-circuit voltage and SCC were used to determine proton and leak conductances. OA caused a marked increase in membrane conductance, allowing the use of a voltage-clamp technique. From SCC data, we were able to estimate the flip-flop rate constants for palmitate (1 ؋ 10 ؊ 6 s ؊ 1 ) and oleate (49 ؋ 10 ؊ 6 s ؊ 1 ) anions. Cholesterol, included in the membrane-forming solution, decreased importantly the leak conductance both in membranes unmodified by FA and in membranes modified by PA added to the bath. Long-chain FA transport across the cell membranes is still a controversial subject. There are two lines of evidence pointing to either a simple diffusional mechanism (1) or a protein-mediated process (2). Through the diffusional mechanism, FA transport is described as being coupled to proton transport, as the protonated (uncharged) form of the FA diffuses better in the hydrophobic interior of the lipid bilayer (3). In this way, FA flip-flop would act as a proton shuttle.On the other hand, the presence of FA in the membrane may enhance proton transport independently of this shuttle mechanism, mainly in the case of unsaturated fatty acids, which reduce membrane order (4), and so could increase proton transport through aqueous defects. Cholesterol, through its membrane-ordering effect (5), could modulate this shuttle-independent proton pathway.The issue of long-chain FA translocation across cell membranes has been dealt with using many approaches (6-8). In biomimetic systems, indirect evidence of FAmediated proton transfer has been obtained mainly from unilamellar vesicles by acidification studies using fluorescent pH-sensitive probes (1).Despite being very sensitive regarding time resolution of the acidification process, studies using vesicles lack information concerning electrical parameters such as transmembrane potential difference, proton-associated electrical currents, and electrical conductance. On the other hand, electrical determinations of FA effects on proton transfer are scant and have been based on membrane conductance measurements (9), suggesting that FAs increase proton transport across the lipid bilayer. In such studies, the membrane-unspecific or leak conductance contributes importantly to the measured conductance and constitutes a major source of indeterminacy.The problem in measuring total membrane conductance arises when the membrane is subjected to an externally applied field, which drives protons, through a protonselective pathway, and other ions, through a nonspecific (leak) pathway. Identifying separately the proton and leak conductances i...

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Section: Membranes Modified By Fa In the Bathsupporting

confidence: 88%

Fatty acid flip-flop and proton transport determined by short-circuit current in planar bilayers

Brunaldi

Arcísio-Miranda

Abdulkader

et al. 2005

Journal of Lipid Research

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“…These changes usually result in increased membrane permeability (36), cause membrane fusion (37), and eventually lead to lamellar disruption (38). In contrast, Chol in phospholipid lamellae behaves as if it were a truncated cone (5), and its incorporation into PC bilayers reduces membrane permeability, broadens the gel to liquid-crystalline phase transition, and decreases average molecular surface areas (39)(40)(41)(42). It is not only that lysoPC and Chol affect phospholipid bilayers quite differently, but when both are present in similar proportions, they appear to counteract each other's effect (11,24,32,43).…”

Section: Resultsmentioning

confidence: 99%

Complementary molecular shapes and additivity of the packing parameter of lipids.

Kumar

1991

Proc. Natl. Acad. Sci. U.S.A.

171

132

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Physical dimensions of a membrane component influence its phase preference upon hydration. A dimensionless packing parameter, S, given by S = V/al, where V is the hydrocarbon volume, a is the area of the head group, and I is the critical length of the hydrocarbon chain, is useful in determining the phase preference of a lipid, and the value of S usually lies between 0.5 and 1 for bilayers. Here, the value of S is calculated for phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) as a function of chain length, and it is shown that diacylPC having an S value of <0.74 does not form bilayers. For example, diacylPC, up to a chain length of eight carbon atoms, forms only micelles, whereas higher homologs with S > 0.74 form bilayers. It is also shown that when lipid molecules having complementary shapes associate, the value of S becomes additive. Using the additivity of S, a number of experimental results for lipid mixtures can be explained. For example, lysoPC and cholesterol form lamellar structures between 45 and "40 mol% cholesterol, and the additive value of S for this region is between 0.74 and 1. Similarly, the additivity of S shows that the maximum amount of cholesterol that can be incorporated into PC bilayers is 50 mol%, in agreement with experimental studies.Molecular shape is an important consideration in membrane modeling. Based on the physical dimensions of a membrane component, its phase presence upon hydration and its location in the membrane can often be predicted. Taking into account interaction free energies, molecular geometry, and entropy, theoreticians have developed a dimensionless packing parameter, S, that is useful in determining the size and shape of lipid aggregates. S is given by S = V/al, where V is the hydrocarbon volume, a is the area of head group, and 1 is the critical length of the hydrocarbon chain (1-3). a, V, and I are all estimable or measurable (4), and the value of S can be calculated. The value of S determines the aggregate formed by lipids or any amphiphiles upon hydration. It has been shown that lipids aggregate to form spherical micelles (S

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“…There is, however, no experimental support for a direct interaction between phospholipid and sterol. Studies with phospholipids lacking the ester linkage, as ether and alkyl derivatives, indicate that a direct hydrogen bonding is not required for the condensing effect of cholesterol [33][34][35][36]. Certain critical proportions of cholesterol to phospholipid have been described.…”

Section: Discussionmentioning

confidence: 99%

The effect of the sterol oxygen function on the interaction with phospholipids

Demel

Lala

Kumari

et al. 1984

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The effect of cholesteryi ethers (namely cholesteryl methyl ether, cholesteryi ethyl ether, cholesteryl n-propyl ether, cholesteryi isopropyl ether, cholesteryi butyl ether, cholesteryl methoxymethyl ether, cholesteryl (2'-hydroxy)-3-ethyl ether) and cholesteryl ester (namely cholesteryi acetate) is tested on the interaction with phosphatidylcholines in liquid-crystalline and crystalline state. The interfacial properties of sterols are tested at the air-water interface. The cholesteryl ethers show a reduced interracial stability with increasing hydrophobicity of the ether-linked moiety. The interaction between the sterol derivatives and phospholipids in mixed monolayers is indicated by measuring the deviation from the simple addivity rule (condensing effect). An interaction is found only for cholesteryl (2'-hydroxy)-3-ethyl ether, cholesteryl methyl ether and cholesteryl ethyl ether. These sterols also reduce the glucose permeability of liposomal membranes in this order. In this respect cholesteryl (2'-hydroxy)-3-ethyl ether is as effective as cholesterol. Cholesteryl methyl ether and cholesteryl ethyl ether show 62 and 33 percent of the effect observed with cholesterol. The effect of the sterol derivatives on the gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine is measured by differential scanning calorimetry. Cholesteryl methyl ether, cholesteryl ethyl ether, and cholesteryl (2'-hydroxy)-3-ethyl ether reduce the energy content of the phase transition nearly as effective as cholesterol, cholesteryl n-propyl ether has only a small effect. Although cholesteryl acetate, and cholesteryl methoxymethyl ether have no condensing or permeability-reducing effect, they have a considerable effect on the gel-to-liquid-crystalline phase transition. Cholesteryi isopropyl ether and cholesteryl butyl ether have no effect. It is concluded that a free 30-hydroxy group is not a prerequisite to observe a sterol-like effect in membranes. However, the interfacial stability and the orientation of the sterol and oxygen moiety at the sterol 3-position are important.

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Effects of sterols on permeability and phase transitions of bilayers from phosphatidylcholines lacking acyl groups

Cited by 67 publications

References 35 publications

Fatty acid flip-flop and proton transport determined by short-circuit current in planar bilayers

Fatty acid flip-flop and proton transport determined by short-circuit current in planar bilayers

Complementary molecular shapes and additivity of the packing parameter of lipids.

The effect of the sterol oxygen function on the interaction with phospholipids

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