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1.
Amphotericin B (AmB) is one of the main antibiotics applied in treatment of deep-seated mycotic infections. Tensiometric technique has been applied to monitor binding of AmB, from the water subphase, to the lipid monomolecular layers, formed with dipalmitoylphosphatidylcholine at the air-water interface. Time dependencies of surface pressure in the monolayers demonstrate strong enhancement of AmB binding to monolayers brought about by sterols present in the membranes. The monolayers have been deposited to a solid support and examined by means of FTIR spectroscopy. FTIR measurements show that majority of the AmB molecules which bind to the membranes are localized in the polar headgroup region. The results of the linear dichroism-FTIR measurements are consistent with the microscopic picture according to which the molecules of the membrane-bound AmB are distributed among two orientational fractions: one horizontal and one vertical with respect to the plane of the membrane (59% versus 41% respectively, in the case of the membrane formed with the pure lipid without sterols). The presence of cholesterol in the membranes (50 mol% with respect to lipid) slightly affects such a distribution (53% horizontal versus 47% vertical) but the presence of ergosterol has a pronounced effect in the increase in population of the fraction of horizontally bound AmB (85% horizontal vs. 15% vertical). The results of the measurements indicate that mode of action of the AmB consists in disruption of the polar headgroup region of biomembranes, brought about by the AmB molecules bound horizontally with respect to the plane of the membrane. 相似文献
2.
Langmuir monolayers of amphotericin B (AmB) were investigated by recording π-A isotherms under different pH conditions. To gain a better insight into antibiotic-membrane interactions they were monitored by use of the ATR-FTIR spectroscopy. It was observed for AmB monolayers that the limiting molecular area was larger at high than at neutral pH. Analysis of FTIR spectra at different pH revealed substantial differences, depending on ionic state, for different orientations of AmB molecules. These results enable better understanding of the participation of functional groups in the interactions between AmB and sterol-containing DPPC membranes. AmB molecules incorporated into two-component lipid monolayers bind strongly to the ergosterol-rich membrane (maximum penetration surface pressures ca 35?mN/m). The FTIR spectra revealed that the ionic state of AmB and the presence of sterols led to changes in membrane fluidity and molecular packing of the AmB molecules in the lipid membranes. These investigations should be further investigated to discover the molecular mechanism responsible for the mode of action AmB in biological systems. 相似文献
3.
Amphotericin B (AmB) is a popular antibiotic applied in treatment of deep-seated mycotic infections. The mode of action of AmB is based upon interactions with biomembranes but exact binding properties of the antibiotic to the lipid membranes still remain obscure. Effect of incorporation of AmB into egg yolk phosphatidylcholine membranes in the concentration range from 0.01 to 5 mol% on structural and dynamic properties of lipid bilayers was studied with application of small-angle neutron scattering, X-ray diffractometry and Fourier-transform infrared spectroscopy (FTIR). The results of the experiments show that AmB is located predominantly in the headgroup region of the membranes at concentrations below 1 mol%. The process of AmB aggregation, at concentrations above 1 mol%, is associated with ordering effect within the acyl chain region and therefore indicates incorporation of AmB into the hydrophobic membrane core. 相似文献
4.
Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of fungal infections. According to the general understanding, the mode of action of AmB is directly related to the molecular organization of the drug in the lipid environment, in particular to the formation of pore-like molecular aggregates. Electronic absorption and fluorescence techniques were applied to investigate formation of molecular aggregates of AmB in the lipid environment of liposomes and monomolecular layers formed at the argon-water interface. It appears that AmB dimers, stabilized by van der Waals interactions, are present in the membrane environment along with the aggregates formed by a greater number of molecules. Linear dichroism measurements reveal that AmB is distributed between two fractions of molecules, differently oriented with respect to the bilayer. Molecules in one fraction remain parallel to the plane of the membrane and molecules in the other one are perpendicular. Scanning Force Microscopy imaging of the surface topography of the monolayers formed with AmB in the presence of lipids reveals formation of pore-like structures characterized by the external diameter close to 17 A and the internal diameter close to 6 A. All the findings are discussed in terms of importance of the molecular organization of AmB in the pharmacological action, as well as of the toxic side effects of the drug. 相似文献
5.
《Biochemical and biophysical research communications》2020,521(3):699-705
AmB is an antifungal drug of polyene. Although it is prone to nephrotoxicity, it is still the gold standard in the clinical treatment of fungal infection. Sterol plays a decisive role in the drug activity of AmB. The antifungal activity of AmB depends on ergosterol in fungal membranes, and its toxicity is related to cholesterol in mammalian membranes. At the same time, AmB interacts with biofilms, leading to a significant loss of potassium ions and affecting the transport of potassium ions across membranes. Meanwhile, metal cation may also affect AmB molecules’ aggregation on the membrane. This paper mainly studied the effects of different concentrations of potassium ions on the interactions between AmB and lipid monolayers containing cholesterol or ergosterol and explored the differences in the impact of varying potassium ions on the drug activity of AmB on monolayers rich in these two kinds of sterols. The results show that potassium ions caused the collapse of lipid monolayer and lipid-AmB monolayer to disappear. The limiting molecular area of these monolayers also increased due to potassium ions. The limiting molecular area of the monolayer in the presence of ergosterol has a great difference in the different concentration of potassium ions, which is different from that in the presence of cholesterol. The presence of potassium ions, regardless of the intensity of K+ ions, increased the maximum elastic modulus of the lipid/sterol monolayer with and without AmB. The presence of potassium ions reduced the influence of AmB on the stability of the lipid monolayer containing cholesterol. The impact of AmB on the stability of the lipid monolayer containing ergosterol was related to the concentration of potassium ions. The potassium ions increased the area of the ordered “island” region on the lipid-AmB monolayer containing cholesterol, and the boundary of the microregion produced different degrees of curvature. However, on the lipid/ergosterol monolayer, 5 mM and 10 mM potassium ions made the holes caused by AmB more denser, and the diameter of holes become larger. These results can help to improve the effect of potassium ions on the transmembrane transport of substances affected by AmB. The results will provide a basis for further exploration of the effect mechanism of metal ions on the antifungal activity of polyene drugs. 相似文献
6.
Amphotericin B (AmB) is the most widely used antibiotic to treat systemic fungal infections. However, the molecular mechanism of its activity is still not completely understood. In the present work we have used FTIR spectroscopy to investigate the conformational state of the aliphatic chains of DPPC liposomes using the 2850 cm(-1) band, associated with the methylene symmetric stretching mode. The liposomes were either binary mixtures of the lipid with AmB, cholesterol or ergosterol, or ternary systems of these constituents. The two sterols contribute to an ordering of the aliphatic chains of the lipid, this ordering being slightly more important with ergosterol. In the gel state, AmB does not change the conformational order of DPPC even at high concentration. In the fluid phase, however, the drug clearly structures its lipid environment. Our results show that AmB can initiate a redistribution of the ergosterol in the plane of the membrane, but not of the cholesterol molecules, which might constitute an additional mechanism to explain the activity of the antibiotic. 相似文献
7.
Agnieszka Sujak Janina Gabrielska Piotr Mazurek Wies?aw I. Gruszecki 《生物化学与生物物理学报:生物膜》2005,1712(1):17-28
Polar carotenoid pigment - canthaxanthin - has been found to interfere with the organization of biological membranes, in particular of the retina membranes of an eye of primates. The organization of lipid membranes formed with dipalmitoylphosphatidylcholine (DPPC) and egg yolk phosphatidylcholine containing canthaxanthin was studied by means of several techniques including: electronic absorption spectroscopy, linear dichroism, X-ray diffractometry, 1H-NMR spectroscopy and FTIR spectroscopy. It appears that canthaxanthin present in the lipid membranes at relatively low concentration (below 1 mol% with respect to lipid) modifies significantly physical properties of the membranes. In particular, canthaxanthin (i) exerts restrictions to the segmental molecular motion of lipid molecules both in the headgroup region and in the hydrophobic core of the bilayer, (ii) promotes extended conformation of alkyl lipid chains, (iii) modifies the surface of the lipid membranes (in particular in the gel state, Lβ´) and promotes the aggregation of lipid vesicles. It is concluded that canthaxanthin incorporated into lipid membranes is distributed among two pools: one spanning the lipid bilayer roughly perpendicularly to the surface of the membrane and one parallel to the membrane, localized in the headgroup region. The population of the horizontal fraction increases with the increase in the concentration of the pigment in the lipid phase. Such a conclusion is supported by the linear dichroism analysis of the oriented lipid multibilayers containing canthaxanthin: The mean angle between the dipole transition moment and the axis normal to the plane of the membrane was determined as 20 ± 3° at 0.5 mol% and 47 ± 3° at 2 mol% canthaxanthin. The analysis of the absorption spectra of canthaxanthin in the lipid phase and 1H-NMR spectra of lipids point to the exceptionally low aggregation threshold of the pigment in the membrane environment (∼1 mol%). All results demonstrate a very strong modifying effect of canthaxanthin with respect to the dynamic and structural properties of lipid membranes. 相似文献
8.
Amphotericin B (AmB) is considered the gold-standard in the treatment of serious systemic mycoses despite its numerous adverse effects. Both the mechanism of antifungal action and the toxicity of this drug are dependent on its molecular organization. The effect of AmB on the organization of lipid membranes formed with dipalmitoylphosphatidylcholine (DPPC) was studied with application of the Langmuir-Blodgett technique and ATR-FTIR spectroscopy. The aim of this research was to analyze the physical interactions leading to the formation of aggregated forms of AmB molecules in one-component monolayers and lipid multibilayers. Analysis of FTIR spectra of two-component multibilayers suggests the possibility the mutual reorientation of the amino-sugar moiety (mycosamine) and macrolide ring. This effect may be significant in the explanation of the aggregation processes of AmB in biological systems. 相似文献
9.
Daniel Michał Kamiński 《European biophysics journal : EBJ》2014,43(10-11):453-467
In the past decade substantial progress has been made in understanding the organization and biological activity of amphotericin B (AmB) in the presence of sterols in lipid environments. This review concentrates mainly on interactions of AmB with lipids and sterols, AmB channel formation in membranes, AmB aggregation, AmB modifications important for understanding its biological activity, and AmB models explaining its mechanism of action. Most of the reviewed studies concern monolayers at the water–gas interface, monolayers deposited on a solid substrate by use of the Langmuir–Blodgett technique, micelles, vesicles, and multi-bilayers. Liposomal AmB formulations and drug delivery are intentionally omitted, because several reviews dedicated to this subject are already available. 相似文献
10.
Amphotericin B (AmB) is a well-known polyene macrolide antibiotic used to treat systemic fungal infections. AmB targets more efficiently fungal than animal membranes. However, there are only minor differences in the mode of action of AmB against both types of membranes, which is a source of AmB toxicity. In this work, we analyzed interactions of two low toxic derivatives of AmB (SAmE and PAmE), synthesized in our laboratory, with lipid membranes. Molecular dynamics simulations of the lipid bilayers containing ergosterol (fungal cells) or cholesterol (animal cells) and the studied antibiotic molecules were performed to compare the structural and dynamic properties of AmB derivatives and the parent drug inside the membrane. A number of differences was found for AmB and its derivatives' behavior in cholesterol- and ergosterol-containing membranes. We found that PAmE and SAmE can penetrate deeper into the hydrophobic region of the membrane compared to AmB. Modification of the amino and carboxyl group of AmB also resulted in the conformational transition within the antibiotic's polar head. Wobbling dynamics differentiation, depending on the sterol present, was discovered for the AmB derivatives. These differences may be interpreted as molecular factors responsible for the improved selectivity observed macroscopically for the studied AmB derivatives. 相似文献
11.
Jacek Czub 《生物化学与生物物理学报:生物膜》2007,1768(10):2616-2626
Amphotericin B (AmB) is a well-known polyene macrolide antibiotic used to treat systemic fungal infections. AmB targets more efficiently fungal than animal membranes. However, there are only minor differences in the mode of action of AmB against both types of membranes, which is a source of AmB toxicity. In this work, we analyzed interactions of two low toxic derivatives of AmB (SAmE and PAmE), synthesized in our laboratory, with lipid membranes. Molecular dynamics simulations of the lipid bilayers containing ergosterol (fungal cells) or cholesterol (animal cells) and the studied antibiotic molecules were performed to compare the structural and dynamic properties of AmB derivatives and the parent drug inside the membrane. A number of differences was found for AmB and its derivatives' behavior in cholesterol- and ergosterol-containing membranes. We found that PAmE and SAmE can penetrate deeper into the hydrophobic region of the membrane compared to AmB. Modification of the amino and carboxyl group of AmB also resulted in the conformational transition within the antibiotic's polar head. Wobbling dynamics differentiation, depending on the sterol present, was discovered for the AmB derivatives. These differences may be interpreted as molecular factors responsible for the improved selectivity observed macroscopically for the studied AmB derivatives. 相似文献
12.
Amphotericin B (AmB) is a polyene macrolide antibiotic used to treat systemic fungal infections. The molecular mechanism of AmB action is still only partly characterized. AmB interacts with cell-membrane components and forms membrane channels that eventually lead to cell death. The interaction between AmB and the membrane surface can be regarded as the first (presumably crucial) step on the way to channel formation. In this study molecular dynamics simulations were performed for an AmB–lipid bilayer model in order to characterize the molecular aspects of AmB–membrane interactions. The system studied contained a box of 200 dimyristoylphosphatidylcholine (DMPC) molecules, a single AmB molecule placed on the surface of the lipid bilayer and 8,065 water molecules. Two molecular dynamics simulations (NVT ensemble), each lasting 1 ns, were performed for the model studied. Two different programs, CHARMM and NAMD2, were used in order to test simulation conditions. The analysis of MD trajectories brought interesting information concerning interactions between polar groups of AmB and both DMPC and water molecules. Our studies show that AmB preferentially took a vertical position, perpendicular to the membrane surface, with no propensity to enter the membrane. Our finding may suggest that a single AmB molecule entering the membrane is very unlikely.Figure The figure presents the whole structure of the system simulated—starting point. AmB is presented as a space-filling model, DMPC molecules—green sticks, water molecules—red sticks 相似文献
13.
Cholesterol, stigmastanol, and stigmastanyl-phosphorylcholine (ST-PC) were incorporated into model membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). POPC and ST-PC were deuterated at the lipid headgroup, DOPC at the cis-double bonds. The influence of the three sterols on the motion and conformation of the lipid headgroups and the hydrocarbon chains was monitored with 2H- and 31P-NMR. All three sterols were freely miscible with the lipid matrix in concentrations of up to 50 mol% without inducing phase separations or nonbilayer structures. However, the molecules exert quite different effects on the phospholipid bilayer. Cholesterol and stigmastanol are largely buried in the hydrocarbon part of the membrane, distinctly restricting the flexing motions of the fatty acyl chains whereas the conformation of the phospholipid headgroups is little affected. In contrast, ST-PC is anchored with its headgroup in the layer of phospholipid dipoles, preventing an extensive penetration of the sterol ring into the hydrocarbon layer. Hence ST-PC has almost no effect on the hydrocarbon chains but induces a characteristic conformational change of the phospholipid headgroups. The 2H- and 31P-NMR spectra of mixed phospholipid/ST-PC membranes further demonstrate that the PC headgroup of ST-PC has a similar orientation as the surrounding phosphatidylcholine headgroups. For both types of molecules the -P-N+ dipole is essentially parallel to the membrane surface. Addition of ST-PC induces a small rotation of the POPC headgroup towards the water phase. 相似文献
14.
Yilma S Cannon-Sykora J Samoylov A Lo T Liu N Brinker CJ Neely WC Vodyanoy V 《Biosensors & bioelectronics》2007,22(7):1359-1367
The antimycotic activity of amphotericin B (AmB) depends on its ability to make complexes sterols to form ion channels that cause membrane leakage. To study this phenomenon, surface pressure (pi) as a function of surface area (A) and pi-A hysteresis were measured in monolayers of AmB-cholesterol mixtures on the water-air interface. The most stable monolayers were produced from molecules of AmB and cholesterol with 2:1 stoichiometry. At this ratio, AmB and cholesterol interact to form ion channels in lipid bilayers with millisecond dwell times and conductances of 4-400 pS. The AmB-cholesterol complexes assemble in three, four, etc., subunit aggregates to form ion channels of diverse and large-conductances. Their I-V characteristics were linear over a range of +/-200 mV. The channel currents were inhibited by the addition of tetraethylammonium (TEA), potassium channel blocker, to the cis-side of the membrane. Likewise, AmB-cholesterol complexes reconstituted in membrane-coated nanoporous silicon dioxide surfaces showed single channel behavior with large amplitudes at various voltages. Large-conductance ion channels show great promise for use in biosensors on solid supports. 相似文献
15.
Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. II. Suppression of tetraphenylborate conductance and changes of interfacial potentials.
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It has been shown that the blocking of negatively charged tetraphenylborate ion transport in phosphatidylcholine (PC)-cholesterol membranes by the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is dominated by suppression of TPhB- diffusion across the membrane interior, rather than by the decrease of adsorption of TPhB- ions at the membrane surface. The blocking effect can be associated with the decrease of electric potential inside the membrane with respect to that of the aqueous medium, this decreases being proportional to the concentration of 2,4-D in the aqueous solution. It has been estimated that 25 - 30% of the total 2,4-D-induced change of the potential difference is between the plane of absorption of TPhB- and the aqueous solution, and the remaining fraction is between the membrane interior and the absorption plane. The results of this study support the dipolar hypothesis of 2,4-D action in lipid membranes. These conclusions are further supported by measurements changes of electric potential difference across air/water and air/lipid monolayer/water interfaces. It has been found that the electric potential of the nonpolar side of the interface decreases in the presence of neutral molecules of 2,4-D and that this effect becomes more prominent in presence of electrolyte. We have confirmed that PC-cholesterol monolayer cannot be considered as a model for half of the bilayer membrane because of the disagreement between the changes of the interfacial potential difference of PC-cholesterol monolayers and those determined from studied of transport of positive and negative ions across bilayer membranes. In contract, we have found close agreement between the 2,4-D-induced changes of electric potential of the lipid hydrocarbon region in glycerolmonooleate (GMO) membranes and GMO monolayers. We suggest that the action of 2,4-D in lipid membranes is not associated with the changes of orientation of dipoles of lipids constituting the membranes, but rather with a layer of 2,4-D molecules absorbed at the nonpolar/polar membrane boundary. 相似文献
16.
Ceramide selectively displaces cholesterol from ordered lipid domains (rafts): implications for lipid raft structure and function 总被引:11,自引:0,他引:11
Ceramide is a membrane lipid involved in a number of crucial biological processes. Recent evidence suggests that ceramide is likely to reside and function within lipid rafts; ordered sphingolipid and cholesterol-rich lipid domains believed to exist within many eukaryotic cell membranes. Using lipid vesicles containing co-existing raft domains and disordered fluid domains, we find that natural and saturated synthetic ceramides displace sterols from rafts. Other raft lipids remain raft-associated in the presence of ceramide, showing displacement is relatively specific for sterols. Like cholesterol-containing rafts, ceramide-rich "rafts" remain in a highly ordered state. Comparison of the sterol-displacing abilities of natural ceramides with those of saturated diglycerides and an unsaturated ceramide demonstrates that tight lipid packing is critical for sterol displacement by ceramide. Based on these results, and the fact that cholesterol and ceramides both have small polar headgroups, we propose that ceramides and cholesterol compete for association with rafts because of a limited capacity of raft lipids with large headgroups to accommodate small headgroup lipids in a manner that prevents unfavorable contact between the hydrocarbon groups of the small headgroup lipids and the surrounding aqueous environment. Minimizing the exposure of cholesterol and ceramide to water may be a strong driving force for the association of other molecules with rafts. Furthermore, displacement of sterol from rafts by ceramide is very likely to have marked effects upon raft structure and function, altering liquid ordered properties as well as molecular composition. In this regard, certain previously observed physiological processes may be a result of displacement. In particular, a direct connection to the previously observed sphingomyelinase-induced displacement of cholesterol from plasma membranes in cells is proposed. 相似文献
17.
Suwalsky M Villena F Norris B Cuevas F Sotomayor CP 《Journal of inorganic biochemistry》2004,98(6):1061-1066
The structural effects of cadmium on cell membranes were studied through the interaction of Cd(2+) ions with human erythrocytes and their isolated unsealed membranes (IUM). Studies were carried out by scanning electron microscopy and fluorescence spectroscopy, respectively. Cd(2+) induced shape changes in erythrocytes, which took the form of echinocytes. According to the bilayer couple hypothesis, this result meant that Cd(2+) ions located in the outer monolayer of the erythrocyte membrane. Fluorescence spectroscopy measurements in IUM indicated a disordering effect at both the polar headgroup and the acyl chain packing arrangements of the membrane phospholipid bilayer. Cd(2+) ions also interacted with molecular models of the erythrocyte membrane consisting in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representing classes of phospholipids located in the outer and inner monolayers the erythrocyte membrane, respectively. X-ray diffraction indicated that Cd(2+) ions induced structural perturbation of the polar headgroup and of the hydrophobic acyl regions of DMPC, while the effects of cadmium on DMPE bilayers were much milder. This conclusion is supported by fluorescence spectroscopy measurements on DMPC large unilamellar vesicles (LUV). All these findings point to the important role of phospholipid bilayers in the interaction of cadmium on cell membranes. 相似文献
18.
Canthaxanthin is a carotenoid pigment of physiological importance owing to potential modulation of the dynamic and structural properties of biomembranes. The effect of canthaxanthin on the organization of lipid membranes formed with dipalmitoylphosphatidylcholine (DPPC) was studied with application of monomolecular layer technique, FTIR spectroscopy and linear dichroism-FTIR. The specific molecular areas of the two-component monomolecular layers of canthaxanthin-DPPC show pronounced underadditivity in the concentration range below 2 mol% carotenoid with respect to the lipid, corresponding to the monomeric organization of the pigment. Additionally, the analysis of the FTIR spectra of the two-component monolayers deposited to the solid support shows that organization of the carotenoid in the lipid monolayer is governed primarily by van der Waals interactions between the pigment chromophore and lipid alkyl chains. This interaction is responsible for an ordering effect of canthaxanthin with respect to lipids. Analysis of FTIR spectra of two-component monolayers suggests the possibility of hydrogen bonding between the lipid polar headgroups and the keto groups of canthaxanthin via water bridges. 相似文献
19.
Canthaxanthin is a carotenoid pigment of physiological importance owing to potential modulation of the dynamic and structural properties of biomembranes. The effect of canthaxanthin on the organization of lipid membranes formed with dipalmitoylphosphatidylcholine (DPPC) was studied with application of monomolecular layer technique, FTIR spectroscopy and linear dichroism-FTIR. The specific molecular areas of the two-component monomolecular layers of canthaxanthin-DPPC show pronounced underadditivity in the concentration range below 2 mol% carotenoid with respect to the lipid, corresponding to the monomeric organization of the pigment. Additionally, the analysis of the FTIR spectra of the two-component monolayers deposited to the solid support shows that organization of the carotenoid in the lipid monolayer is governed primarily by van der Waals interactions between the pigment chromophore and lipid alkyl chains. This interaction is responsible for an ordering effect of canthaxanthin with respect to lipids. Analysis of FTIR spectra of two-component monolayers suggests the possibility of hydrogen bonding between the lipid polar headgroups and the keto groups of canthaxanthin via water bridges. 相似文献
20.
Sphingolipid partitioning into ordered domains in cholesterol-free and cholesterol-containing lipid bilayers
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We have used fluorescence-quenching measurements to characterize the partitioning of a variety of indolyl-labeled phospho- and sphingolipids between gel or liquid-ordered and liquid-disordered lipid domains in several types of lipid bilayers where such domains coexist. In both cholesterol-free and cholesterol-containing lipid mixtures, sphingolipids with diverse polar headgroups (ranging from sphingomyelin and monoglycosylceramides to ganglioside GM1) show a net preference for partitioning into ordered domains, which varies modestly in magnitude with varying headgroup structure. The affinities of different sphingolipids for ordered lipid domains do not vary in a consistent manner with the size or other simple structural properties of the polar headgroup, such that for example ganglioside GM1 partitions between ordered and disordered lipid domains in a manner very similar to sphingomyelin. Ceramide exhibits a dramatically higher affinity for ordered lipid domains in both cholesterol-free and cholesterol-containing bilayers than do other sphingolipids. Our findings suggest that sphingolipids with a variety of headgroup structures will be enriched by substantial factors in liquid-ordered versus liquid-disordered regions of membranes, in a manner that is only modestly dependent on the nature of the polar headgroup. Ceramide is predicted to show a very strong enrichment in such domains, supporting previous suggestions that ceramide-mediated signaling may be compartmentalized to liquid-ordered (raft and raft-related) domains in the plasma membrane. 相似文献