Studies on the anomalous thermotropic behavior of aqueous dispersions of dipalmitoylphosphatidylcholine-cholesterol mixtures

Abstract

Examination of the thermotropic behavior of aqueous dispersions of dipalmitoylphosphatidylcholine-cholesterol mixtures by high-sensitivity scanning calorimetry has revealed that the phospholipid gel to liquid-crystalline phase transition consists of two components. One, a relatively sharp transition centered at 39.6-40.7 degrees C, exhibits a transition enthalpy change which decreases linearly with increasing cholesterol content, approaching zero at a cholesterol content of about 25 mol %. The other, a broad, lower intensity transition centered at approximately 41.5 degrees C for cholesterol concentrations of 20 mol %, displays an enthalpy change which is maximal at about 20-25 mol % cholesterol and which decreases as the cholesterol content decreases to zero or increases above 25 mol %. The origin of these two transitions is discussed in terms of a separation of these lipid mixtures into cholesterol-rich and cholesterol-poor domains.

Phosphatidylcholesterol bilayers. A model for phospholipid-cholesterol interaction

“…The resulting sample furnished a calcium salt of which the aqueous dispersions showed a phase transition with a significantly larger cooperative unit (n > 250), although other transition parameters remained virtually unchanged. The thermotropic phase transition characteristics of divalent metal salts of phosphatidylcholesterol are analogous to those previously observed for dipalmitoyl phosphatidylcholine [3,4] and dipalmitoyl phosphatidic acid [15], all in aqueous dispersions. Thus, it appears that, under certain circumstances, the phosphatidylcholesterol molecules in water axe indeed able to form a gel phase that undergoes a highly cooperative transition to a liquid crystalline phase, It is not entirely ruled out that the monovalent cation salts of phosphatidylcholesterol give rise to phase transitions of low cooperativity, and hence produce very broad peaks which are undetectable by our experimental techniques.…”

“…There is general agreement that cholesterol is anisotropically oriented parallel to phospholipid acyl chains with the 3fi-OH group near the glycerol backbone, and that the sterol restricts freedom of motion of the acyl chains. The addition of less than 25 mol% of cholesterol to certain saturated phospholipids results in the separation of a sterol-deficient phase from a sterol-rich phase [3,4]. In such systems, the gross bilayer organization is retained only up to a maximum incorporation of 50 mol% of cholesterol.…”

Fluorescence lifetime distributions of 1,6-diphenyl-1,3,5-hexatriene reveal the effect of cholesterol on the microheterogeneity of erythrocyte membrane

“…In lipid mixtures below the phase transition, cholesterol can induce a phase separation, giving rise to cholesterol-rich and cholesterol-poor phases [15,16]. Moreover, the enthalpy and the cooperativity of the gel-to-hquid-crystalline phase transition is reduced by increasing cholesterol concentrations [17]. This effect is also observed for mixed chain phospholipids [18].…”

Membrane Organization at Low Cholesterol Concentrations: A Study Using 7-Nitrobenz-2-oxa-1,3-diazol-4-yl-Labeled Cholesterol

“…All other conditions are as in Figure 3. tions (Estep et al, 1978;Vist & Davis, 1990;McMullen et al, 1993;Harris et al, 1995). Since there are various intracellular organelles such as the endoplasmic reticulum and the inner mitochondrial membrane where the cholesterol content is actively maintained at a low level (Yeagle, 1985;Schroeder et al, 1991;Bretscher & Munro, 1993), such local organization of cholesterol at low concentrations may have important functional consequences.…”

“…It has been assumed that cholesterol is distributed uniformly in the bilayer at these concentrations, although the evidence for it is quite tenuous (Estep et al, 1978;Vist & Davis, 1990;McMullen et al, 1993).…”