Structural Determinants of Water Permeability through the Lipid Membrane (original) (raw)
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Journal of Pharmaceutical Sciences, 2013
Permeability data (P lip/w ) for liquid crystalline phospholipid bilayers composed of egg lecithin and dimyristoylphosphatidylcholine (DMPC) are analyzed in terms of a mathematical model that accounts for free surface area and chain-ordering effects in the bilayer as well as size and lipophilicity of the permeating species. Free surface area and chain ordering are largely determined by temperature and cholesterol content of the membrane, molecular size is represented by molecular weight, and lipophilicity of the barrier region is represented by the 1,9-decadiene/water partition coefficient, following earlier work by Xiang, Anderson, and coworkers. A correlating variable χ = MW n σ/(1 −σ) is used to link the results from different membrane systems, where different values of n are tried, and σ denotes a reduced phospholipid density. The group (1 −σ)/σ is a measure of free surface area, but can also be interpreted in terms of free volume. A single exponential function of χ is developed that is able to correlate 39 observations of P lip/w for different compounds in egg lecithin at low density, and 22 observations for acetic acid in DMPC at higher densities, spanning nine orders of magnitude to within an rms error for log 10 P lip/w of 0.20. The best fit found for n = 0.87 ultimately makes χ much closer to the ratio of molecular to free volumes than surface areas. The results serve as a starting point for estimating passive permeability of cell membranes to nonionized solutes as a function of temperature and cholesterol content of the membrane.
Water permeability of bilayer lipid membranes: Sterol-lipid interaction
The Journal of Membrane Biology, 1972
Bilayer lipid membranes were generated in an aqueous medium from synthetic, egg or plant phosphatidyl choline (PC) or from plant monogalactosyl diglyceride (MG). The water permeability of the black membranes was determined by measuring the net volume flux produced by a NaCI gradient. The osmotic permeability coefficient, Pos, was markedly affected by the number of double bonds in the fatty acid conjugates of the lipids: the greater the degree of unsaturation, the higher the value of Pos. The temperature dependence of Po~ of the lipid membranes was studied over a range of 29 to 40 ~ The experimental activation energy, E~, estimated from the linear plots of log (Pos) versus l/T, was significantly higher for MG membranes (17 kcal/mole) than for the various PC membranes (11 to 13 kcal/mole), probably owing to hydrogen bonding between MG and water molecules. In comparison with PC membranes, the membranes generated from PC and cholesterol (1 : 1 molar ratio) had lower Pos but similar E~ values. Likewise, either stigmasterol or fl-sitosterol decreased Po~ of MG membranes, while E a was not affected by the sterols. MG-cholesterol membranes were specifically characterized by a unique value of E a (-36 kcal/mole) thus indicating temperature dependent structural changes. Lipid bilayer membranes are similar to cellular membranes with respect to thickness, electrical capacitance, interracial tension (Tien & Diana, 1968) permeability to urea, glycerol and mannitol (Vreeman, 1966), as well as water permeability and activation energy of water permeation (Hanai & Haydon, 1966; Henn&Thompson, 1969; Price &Thompson, 1969) as affected by vasopressin (Graziani & Livne, 1971). The similarity in water permeability characteristics may indicate a common mechanism of water transport in biological and artificial bilayer membranes. The range of values of water permeability found in various biological systems (0.37 to 400 g/sec according to Dick, 1959) is much wider than that measured in thin lipid membranes. This apparent discrepancy does not necessarily indicate that the artificial lipid membrane is a poor model for water permeation. It may rather reflect the relatively limited variety of lipids used for the study of water permeation through thin lipid membranes.
Theory of Passive Permeability through Lipid Bilayers
The Journal of General Physiology, 2007
Recently measured water permeability through bilayers of different lipids is most strongly correlated with the area per lipid A rather than with other structural quantities such as the thickness. This paper presents a simple three-layer theory that incorporates the area dependence in a physically realistic way and also includes the thickness as a secondary modulating parameter. The theory also includes the well-known strong correlation of permeability upon the partition coeffi cients of general solutes in hydrocarbon environments (Overton's rule). Two mathematical treatments of the theory are given; one model uses discrete chemical kinetics and one model uses the Nernst-Planck continuum equation. The theory is fi t to the recent experiments on water permeability in the accompanying paper.
Journal of pharmaceutical sciences, 2016
The permeability of gel-phase phospholipids is typically about an order of magnitude lower than that of the same compositions in the fluid phase, yet a quantitative description of the ordering factors leading to this difference has been elusive. The present analysis examines these factors with particular focus on the area per phospholipid chain, Ac, and its relationship to the minimum area per molecule in the crystalline state, A0. It is shown that fluid- and gel-phase phospholipid permeabilities can be reconciled by postulating a minimum area per chain Ac,0 = 17.1 Å(2), substantially less than one would estimate by dividing the accepted value A0 = 40.8 Å(2) by 2. An extended data set of phospholipid and phospholipid-cholesterol bilayer permeability data extending over 9 orders of magnitude is analyzed and correlated according to the developed relationship (N = 85, s = 0.3024, r(2) = 0.9332). Individual permeability values are consequently predicted to within an average deviation of...
A comment on the water permeability through planar lipid bilayers
The Journal of General Physiology, 1977
In a recent article, Finkelstein (1976) has shown that the measured water permeability through a lecithin-decane planar bilayer membrane is similar to the calculated permeability through a sheet ofn-hexadecane 50 ,~ thick. That is, the measured water permeability, Pa, was found equal to DKhc/AX, where D is the diffusion constant of water in water, Khe is the waterm-hexadecane partition
Permeability and the hidden area of lipid bilayers
European Biophysics Journal, 2004
The passive water permeability of a lipid vesicle membrane was studied, related to the hydrostatic (not osmotic) pressure difference between the inner and the outer side of the vesicle in a water environment without additives. Each pressure difference was created by sucking a vesicle into a micropipette at a given sucking pressure. The part of the membrane sucked into the micropipette (the projection length) was measured as a function of time. The time dependence can be divided into two intervals. We put forward the idea that smoothing of membrane defects, accompanied by an increase of the membrane area, takes place during the initial time interval, which results in a faster increase of the projection length. In the second time interval the volume of the vesicle decreases due to the permeability of its membrane and the increase of the projection length is slower. The hidden area and the water permeability of a typical lipid bilayer were estimated. The measured permeability, conjugated to the hydrostatic pressure difference, is an order of magnitude higher than the known value of the permeability, conjugated to the osmotic pressure difference. A hypothesis, based on pore formation, is proposed as an explanation of this experimental result.
Biochemistry, 1994
The hydrophobicity profiles across phosphatidylcholine (PC)-cholesterol bilayer membranes were estimated in both frozen liposome suspensions and fluid-phase membranes as a function of alkyl chain length, unsaturation, and cholesterol mole fraction. A series of stearic acid spin labels, with the probe attached to various positions along the alkyl chain, cholesterol-type spin labels (cholestane and androstane spin labels), and Tempo-PC were used to examine depth-dependent changes in local hydrophobicity, which is determined by the extent of water penetration into the membrane. Local hydrophobicity was monitored primarily by observing the z component of the hyperfine interaction tensor (A,) of the nitroxide spin probe in a frozen suspension of the membrane at -150 "C and was further confirmed in the fluid phase by observing the rate of collision of Fe(CN)63-with the spin probe in the membrane using saturation recovery ESR. Saturated-PC membranes show low hydrophobicity (high polarity) across the membrane, comparable to 2-propanol and 1-octanol, even at the membrane center where hydrophobicity is highest. Longer alkyl chains only make the central hydrophobic regions wider without increasing the level of hydrophobicity. Medical College of Wisconsin. I Abbreviations: Ao, isotropic hyperfine constant of the nitroxide spin probe; A,, z-component of the hyperfine interaction tensor of the nitroxide spin probe; ASL, androstane spin label; CSL, cholestane spin label; DXPC (where X = L, M, P, S, 0, and E), dilauroyl-, dimyristoyl-, dipalmitoyl-, distearoyl-, dioleoyl-, and dielaidoylphosphatidylcholine, respectively; EYPC, egg-yolk phosphatidylcholine; n-SASL, n-doxylstearic acid spin label (n = ; PC, L-a-phosphatidylcholine; T-PC, tempocholine phosphatidic acid ester.
Computer simulation study of intermolecular voids in unsaturated phosphatidylcholine lipid bilayers
The Journal of Chemical Physics, 2005
Computer simulation of the liquid crystalline phase of five different hydrated unsaturated phosphadidylcholine ͑PC͒ lipid bilayers, i.e., membranes built up by 18:0/18:19cis PC, 18:0/18:26cis PC, 18:0/18:33cis PC, 18:0/20:46cis PC, and 18:0/22:63cis PC molecules have been performed on the isothermal-isobaric ensemble at 1 atm and 303 K. ͑The notation n : dpcis specifies the lipid tails: n refers to the total number of carbon atoms in the chain, d is the number of the methylene-interrupted double bonds, p denotes the number of carbons between the chain terminal CH 3 group and the nearest double bond, and cis refers to the conformation around the double bonds.͒ The characteristics of the free volume in these systems have been analyzed by means of a generalized version of the Voronoi-Delaunay method ͓M. G. Alinchenko et al., J. Phys. Chem. B 108, 19056 ͑2004͔͒. As a reference system, the hydrated bilayer of the saturated 14:0/14:0 PC molecules ͑dimyristoylphosphatidylcholine͒ has also been analyzed. It has been found that the profiles of the fraction of the free volume across the membrane exhibit a rather complex pattern. This fine structure of the free volume fraction profiles can be interpreted by dividing the membrane into three separate major zones ͑i.e., zones of the aqueous, polar, and apolar parts of the membrane͒ and defining five subzones within these zones according to the average position of various atomic groups in the membrane. The fraction of the free volume in the middle of the membrane is found to increase with increasing unsaturation of the sn-2 chain of the lipid molecule. This is due to the fact that with increasing number of methylene-interrupted double bonds the lipid tails become more flexible, and hence they do not extend to the middle of the membrane. It is found that there are no broad enough preformed channels in the bilayers through which small penetrants, such as water molecules, can readily go through; however, the existing channels can largely facilitate the permeation of these molecules.
Effects of Ether vs. Ester Linkage on Lipid Bilayer Structure and Water Permeability
Biophysical Journal, 2009
The structure and water permeability of bilayers composed of the ether-linked lipid, dihexadecylphosphatidylcholine (DHPC), were studied and compared with the ester-linked lipid, dipalmitoylphosphaditdylcholine (DPPC). Wide angle X-ray scattering on oriented bilayers in the fluid phase indicate that the area per lipid A is slightly larger for DHPC than for DPPC. Low angle X-ray scattering yields A = 65.1 Å 2 for DHPC at 48 • C. LAXS data provide the bending modulus, K C = 4.2 × 10 −13 erg, and the Hamaker parameter H = 7.2 × 10 −14 erg for the van der Waals attractive interaction between neighboring bilayers. For the low temperature phases with ordered hydrocarbon chains, we confirm the transition from a tilted L  gel phase to an untilted, interdigitated L  I phase as the sample hydrates at 20 • C. Our measurement of water permeability, P f = 0.022 cm/s at 48 • C for fluid phase DHPC is slightly smaller than that of DPPC (P f = 0.027 cm/s) at 50 • C, consistent with our triple slab theory of permeability.
Biochemistry, 1989
Well-ordered multilamellar arrays of liquid-crystalline phosphatidylcholine and equimolar phosphatidylcholine-cholesterol bilayers have been formed in the nonaqueous solvents formamide and 1,3-propanediol. The organization of these bilayers and the interactions between apposing bilayer surfaces have been investigated by X-ray diffraction analysis of liposomes compressed by applied osmotic pressures up to 6 X lo7 dyn/cm2 (60 atm). The structure of egg phosphatidylcholine (EPC) bilayers in these solvents is quite different than in water, with the bilayer thickness being largest in water, 3 A narrower in formamide, and 6 narrower in 1,3-propanediol. The incorporation of equimolar cholesterol increases the thickness of EPC bilayers immersed in each solvent, by over 10 A in the case of 1,3-propanediol. The osmotic pressures