Mixtures of cholesterol with stearic (STA), oleic (OA), and linoleic (LA) acids spread as monolayers at the
air/water interface were used as model systems to examine the hypocholesterolemic effect of fatty acids.
Miscibility and interactions between the components of the cholesterol/fatty acid systems were studied basing
on the analysis of surface pressure/area isotherms completed with Brewster angle microscopy images. In
monolayers, STA and cholesterol were found to be immiscible. In contrast, OA and LA were found to form
miscible, but nonideal mixed monolayers with cholesterol. They exhibit negative deviations from ideality in
the surface pressure/area plots. This reflects close-packing arrangements between bulky cholesterol molecule
and the hydrocarbon chains of unsaturated fatty acids. The analysis of the excess free energies of mixing
shows that the maximum negative value of ΔG
exc appears at about X
chol = 0.5−0.7. Thus, the formation of
the most stable 1:1 and 2:1 complexes between cholesterol and an unsaturated fatty acid molecule may account
for the hypocholesterolemic effect of the acids in human organism by complexing free cholesterol, thereby
hindering its deposition on artery walls.
To cite this version:J. Miñones, S. Pais, O. Conde, P. Dynarowicz-Łątka. Interactions between membrane sterols and phospholipids in model mammalian and fungi cellular membranes -A Langmuir monolayer study. Biophysical Chemistry, Elsevier, 2009, 140 (1-3) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A C C E P T E D
π−A isotherms of mixed monolayers composed of cholesterol and amphotericin B (AmB) spread on
aqueous buffers of various pH and temperatures show the existence of interactions between the two
components, which are more pronounced when the mole fraction of AmB is 0.7. As a consequence of the
interactions, the excess areas and excess free energies of mixing are negative at low surface pressures and
positive at high surface pressures. These results suggest that negative deviations of the additivity rule
are due to the formation of a hydrogen-bonded AmB−cholesterol complex in which AmB molecules are
oriented horizontally at the interface and cholesterol molecules lie vertically. The positive excess areas
of mixing at high surface pressures could be due to AmB being less desorbed in the substrate by composition-dependent van der Waals interactions between the apolar moieties of the components, both oriented in
this situation in a vertical position at the A/W interface.
Using the monolayer technique to study the surface behaviour of systems consisting of amphotericin B (AmB) and various sterols, the components were found to interact with each other. The interactions observed are accounted for by postulating that, at low surface pressures, AmB and different sterols form mixed films where the former lies parallel and the latter normal to the air-water interface in such a way that the polar groups in both components establish hydrogen bonds that lead to the formation of an AmB-sterol 'complex' of 2:1 stoichiometry at the interface. At high surface pressures, AmB molecules rearrange themselves normal to the interface; this gives rise to the Van der Waals interactions between non-polar chains of both components that vary with the nature and composition of the system. The occurrence of these hydrophobic interactions prevents the desorption of AmB into the subphase, which is consistent with the positive excess areas of mixing obtained under these surface pressure conditions. Among the four sterols studied, ergosterol exhibits the strongest interaction with AmB and beta-sitosterol the weakest. Cholesterol and stigmasterol show intermediate behaviour.
Analysis of the compression isotherms of ergosterol/amphotericin B (AmB) mixed monolayers spread
on aqueous substrates shows the existence of interactions between the two components at AmB mole
fractions between 0.1 and 0.7. At low surface pressure AmB molecules appear to lie horizontally in the
A/W interface and ergosterol molecules to stand vertically, while at higher surface pressures the molecules
of both components are vertically oriented at the interface.
Mixed Langmuir monolayers of amphotericin B (AmB) and dipalmitoyl phosphatidyl choline (DPPC) were investigated by recording surface pressure-area (π-A) isotherms in addition to Brewster angle microscopy. The analyses of π-A and compressional modulus curves indicate the existence of interactions in the AmB-DPPC system; the greatest were found to occur for a ca. 2:1 AmB/DPPC mixture. For this mixed monolayer (XAmB ) 0.66), the formation of a stable complex, composed of two horizontally oriented AmB molecules and one DPPC molecule in a vertical position, is suggested. For mixtures containing AmB in excess as compared to the stoichiometric mixture for the complex formation (XAmB > 0.66), the filmforming components are miscible and the mixed monolayer consists of AmB-DPPC complexes together with horizontally (at surface pressures below the first transition) or vertically (at pressures above this transition) oriented free AmB molecules. On the other hand, mixtures of AmB-DPPC complex and DPPC in excess (at XAmB < 0.66) were found to be miscible at surface pressures below the second transition. However, the system becomes immiscible at higher surface pressures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.