The barrier domain for solute permeation varies with lipid bilayer phase structure

被引:58
作者
Xiang, TX [1 ]
Xu, YH [1 ]
Anderson, BD [1 ]
机构
[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA
关键词
permeability; partition coefficients; lipid bilayers; group contributions; linear free energy relationships;
D O I
10.1007/s002329900422
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The chemical selectivities of the transport barriers in lipid bilayers varying in composition and phase structure (gel-phase DPPC and DHPC bilayers and liquid-crystalline DPPC/CHOL/50:50 mol% bilayers) have been investigated by determining functional group contributions to transport of a series of alpha-substituted p-toluic acid analogs obtained in vesicle efflux experiments. Linear free energy relationships are established between the free energies of transfer for this series of compounds from water to the barrier domain and corresponding values for their transfer from water into six model bulk solvents (hexadecane, hexadecene, decadiene, chlorobutane, butyl ether, and octanol) determined in partitioning experiments to compare the barrier microenvironment to that in these model solvents. The barrier microenvironment in all bilayers studied is substantially more hydrophobic than octanol, thus establishing the location of the barrier beyond the hydrated headgroup interfacial region, as the interface is expected to be more hydrophilic than octanol. The chemical nature of the barrier domain microenvironment varies with bilayer phase structure. The barrier regions in non-interdigitated DPPC and interdigitated DHPC gel-phase bilayers exhibit some degree of hydrogen-bond acceptor capacity as may occur if these domains lie in the vicinity of the ester/ether linkages between the headgroups and the acyl chains. Intercalation of 50 mol% cholesterol into DPPC bilayers, which induces a phase transition to a liquid-crystalline phase, substantially increases the apparent barrier domain hydrophobicity relative to gel-phase bilayers to a nonhydrogen bonding, hydrocarbonlike environment resembling hexadecene. This result, combined with similar observations in liquid-crystalline egg-PC bilayers (J. Pharm. Sci. (1994), 83:1511-1518), supports the notion that the transition from the gel-phase to liquid-crystalline phase shifts the barrier domain further into the bilayer interior (i.e., deeper within the ordered chain region).
引用
收藏
页码:77 / 90
页数:14
相关论文
共 51 条
[11]   THE PARTITION OF ORGANIC COMPOUNDS BETWEEN HIGHER ALCOHOLS AND WATER [J].
COLLANDER, R .
ACTA CHEMICA SCANDINAVICA, 1951, 5 (05) :774-780
[12]  
Diamond J.M., 1974, J MEMBRANE BIOL, V17, P148
[13]   INTERPRETATION OF NONELECTROLYTE PARTITION-COEFFICIENTS BETWEEN DIMYRISTOYL LECITHIN AND WATER [J].
DIAMOND, JM ;
KATZ, Y .
JOURNAL OF MEMBRANE BIOLOGY, 1974, 17 (02) :121-154
[14]   MOLECULAR VOLUMES AND STOKES-EINSTEIN EQUATION [J].
EDWARD, JT .
JOURNAL OF CHEMICAL EDUCATION, 1970, 47 (04) :261-&
[15]   SURFACE-POTENTIAL STUDIES OF ALKYL-THIOL MONOLAYERS ADSORBED ON GOLD [J].
EVANS, SD ;
ULMAN, A .
CHEMICAL PHYSICS LETTERS, 1990, 170 (5-6) :462-466
[16]   THICKNESS, COMPOSITION AND STRUCTURE OF SOME LIPID BILAYERS AND NATURAL MEMBRANES [J].
FETTIPLACE, R ;
ANDREWS, DM ;
HAYDON, DA .
JOURNAL OF MEMBRANE BIOLOGY, 1971, 5 (03) :277-+
[17]   THE MEMBRANE DIPOLE POTENTIAL IN A TOTAL MEMBRANE-POTENTIAL MODEL - APPLICATIONS TO HYDROPHOBIC ION INTERACTIONS WITH MEMBRANES [J].
FLEWELLING, RF ;
HUBBELL, WL .
BIOPHYSICAL JOURNAL, 1986, 49 (02) :541-552
[18]   MEMBRANE DIPOLE POTENTIALS, HYDRATION FORCES, AND THE ORDERING OF WATER AT MEMBRANE SURFACES [J].
GAWRISCH, K ;
RUSTON, D ;
ZIMMERBERG, J ;
PARSEGIAN, VA ;
RAND, RP ;
FULLER, N .
BIOPHYSICAL JOURNAL, 1992, 61 (05) :1213-1223
[19]   SHAPE OF HYDROPHOBIC BARRIER OF PHOSPHOLIPID BILAYERS (EVIDENCE FOR WATER PENETRATION IN BIOLOGICAL-MEMBRANES) [J].
GRIFFITH, OH ;
DEHLINGER, PJ ;
VAN, SP .
JOURNAL OF MEMBRANE BIOLOGY, 1974, 15 (02) :159-192
[20]   HYDRATION AND ORDER IN LIPID BILAYERS [J].
HO, C ;
SLATER, SJ ;
STUBBS, CD .
BIOCHEMISTRY, 1995, 34 (18) :6188-6195