Abstract
Vesicle ↔ micelle transitions are important phenomena during bile formation and intestinal lipid processing. The hepatocyte canalicular membrane outer leaflet contains appreciable amounts of phosphatidylcholine (PC) and sphingomyelin (SM), and both phospholipids are found in the human diet. Dietary SM enrichment inhibits intestinal cholesterol absorption. We therefore studied detergent-induced vesicle → micelle transitions in SM-PC vesicles. Phase transitions were evaluated by spectrophotometry and cryotransmission electron microscopy (cryo-TEM) after addition of taurocholate (3–7 mM) to SM-PC vesicles (4 mM phospholipid, SM/PC 40%/60%, without or with 1.6 mM cholesterol). After addition of excess (5–7 mM) taurocholate, SM-PC vesicles were more sensitive to micellization than PC vesicles. As shown by sequential cryo-TEM, addition of equimolar (4 mM) taurocholate to SM-PC vesicles induced formation of open vesicles, then (at the absorbance peak) fusion of bilayer fragments into large open structures (around 200 nm diameter) coexisting with some multilamellar or fused vesicles and thread-like micelles and, finally, transformation into an uniform picture with long thread-like micelles. Incorporation of cholesterol in the SM/PC bilayer changed initial vesicular shape from spherical into ellipsoid and profoundly increased detergent resistance. Disk-like micelles and multilamellar vesicles, and then extremely large vesicular structures, were observed by sequential cryo-TEM under these circumstances, with persistently increased absorbance values by spectrophotometry.These findings may be relevant for bile formation and intestinal lipid processing. Inhibition of intestinal cholesterol absorption by dietary SM enrichment may relate to high resistance against bile salt-induced micellization of intestinal lipids in presence of the sphingolipid.
Highlights
Vesicle ↔ micelle transitions are important phenomena during bile formation and intestinal lipid processing
After addition of taurocholate at a concentration of 3 mM (Fig. 1E), increased absorbance persists during the experiment, especially in case of SM-PC vesicles
We have visualized a time-course of bile salt-induced phase transitions with the aid of state-of-the-art cryo-TEM
Summary
Vesicle ↔ micelle transitions are important phenomena during bile formation and intestinal lipid processing. Disk-like micelles and multilamellar vesicles, and extremely large vesicular structures, were observed by sequential cryo-TEM under these circumstances, with persistently increased absorbance values by spectrophotometry These findings may be relevant for bile formation and intestinal lipid processing. Vesicle ↔ micelle transitions have been studied in some detail by turbidity measurements [7, 8], nuclear magnetic resonance [8, 9], and cryotransmission electron microscopy [10, 11] These studies were generally performed with phosphatidylcholine (PC) as the phospholipid [often with PC from egg yolk, which contains 16:0 acyl chains at the sn-1 position and mainly unsaturated (18:1 Ͼ 18:2 Ͼ 20:4) acyl chains at the sn-2 position]. Cholesterol has a high affinity for SM [14,15,16] and is thought to be preferentially located together with this phospholipid in detergent-resistant rafts in the canalicular membrane [17]
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