Condensed Complexes and the Calorimetry of Cholesterol-Phospholipid Bilayers

Abstract

A recent thermodynamic model describes a reversible reaction between cholesterol (C) and phospholipid (P) to form a condensed complex C(nq)P(np). Here q and p are relatively prime integers used to define the stoichiometric composition, and n is a measure of cooperativity. The present study applies this model to the scanning calorimetry of binary mixtures of cholesterol and saturated phosphatidylcholines, especially work by McElhaney and collaborators. These mixtures generally show two heat capacity peaks, a sharp peak and a broad peak. The sharp heat absorption is largely due to the chain melting transition of pure phospholipid. In the present work the broad heat absorption is attributed to the thermal dissociation of complexes. The best fits of the model to the data require the complex formation to be highly cooperative, with cooperativity n = 12. Detailed comparisons are made between model calculations and calorimetric data. A number of unusual features of the data arise naturally in the model. The principal discrepancy between the calculations and experimental results is a spurious calculated heat absorption peak. This discrepancy is related to the reported relative magnitudes of the integrated broad and sharp heat absorption curves.

Accessibility of Cholesterol in Endoplasmic Reticulum Membranes and Activation of SREBP-2 Switch Abruptly at a Common Cholesterol Threshold

“…The hexamer formation of spin labels in cholesterol-containing liposomes may also be relevant to the discussion here (24). The model of cholesterol-phospholipid complexes has been referred to as the "condensed complex" model and has been a useful tool to successfully model phase diagrams, heat capacities, and NMR spectra of cholesterol-containing bilayers (17,25,26). Other models involving attractive interactions between cholesterol and phospholipid could also result in abrupt changes in cholesterol chemical activity.…”

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

“…A molecular basis for the formation of a sterol-rich ordered lipid phase is that cholesterol forms stoichiometic chemical complexes with specific phospholipids, e.g. saturated phosphatidylcholines, such that this chemical interaction depends upon sterol structure [41][42][43]. We previously demonstrated that different oxysterols, e.g.…”

“…In one model, there is liquid-liquid phase separation into phospholipid-rich l d and cholesterol-rich l o domains (size ~ 20-80 nm) where the l o domains increase in size with the cholesterol concentration [40]. In the second model, cholesterol forms stoichiometric condensed complexes with phospholipid, where the phospholipid-cholesterol mixtures are monophasic and the bilayer properties continuously change as a function of cholesterol concentration [41][42][43]. We observed a direct correlation between the mol% cholesterol in isolated rHDL and the mol% cholesterol in the original phospholipid mixture ( Figure 8A).…”

“…The sharp peak is due to the chain melting of pure phospholipid and disappears at ~20-25 mol% cholesterol. Depending on the model, the broad peak has been attributed to the formation of a single l o phase [40] or condensed complexes of cholesterol and phospholipid [41][42][43]. The increase in lipid-free apoA-I and decrease in rHDL formation occurs in the cholesterol concentration range where the thermal transition of the pure phospholipid phase disappears.…”

Characterization of Solid-Supported Dipalmitoylphosphatidylcholine Membranes Containing Cholesterol

“…A plethora of studies have looked at the function of cholesterol in cell membranes and the effect of the addition of cholesterol in altering the intermolecular interactions in biomimetic 1 membrane systems. 3,15,16 For example, phase diagrams of binary and ternary lipid mixtures containing cholesterol are well-documented 17,18 , and studies have also looked at the alteration of membrane mechanical properties due to preferential segregation of cholesterol 2,8 . In terms of high resolution structural characterization, Mills et al 19 quantified changes in the lamellar repeat distance in multilamellar DPPC vesicles with cholesterol using wide angle x-ray scattering.…”