The Effect of Sterol Structure on Membrane Lipid Domains Reveals How Cholesterol Can Induce Lipid Domain Formation

Abstract

Detergent-insoluble membrane domains, enriched in saturated lipids and cholesterol, have been implicated in numerous biological functions. To understand how cholesterol promotes domain formation, the effect of various sterols and sterol derivatives on domain formation in mixtures of the saturated lipid dipalmitoylphosphatidylcholine (DPPC) and a fluorescence quenching analogue of an unsaturated lipid was compared. Quenching measurements demonstrated that several sterols (cholesterol, dihydrocholesterol, epicholesterol, and 25-hydroxycholesterol) promote formation of DPPC-enriched domains. Other sterols and sterol derivatives had little effect on domain formation (cholestane and lanosterol) or, surprisingly, strongly inhibit it (coprostanol, androstenol, cholesterol sulfate, and 4-cholestenone). The effect of sterols on domain formation was closely correlated with their effects on DPPC insolubility. Those sterols that promoted domain formation increased DPPC insolubility, whereas those sterols that inhibit domain formation decreased DPPC insolubility. The effects of sterols on the fluorescence polarization of diphenylhexatriene incorporated into DPPC-containing vesicles were also correlated with sterol structure. These experiments indicate that the effect of sterol on the ability of saturated lipids to form a tightly packed (i.e., tight in the sense that the lipids are closely packed with one another) and ordered state is the key to their effect on domain formation. Those sterols that promote tight packing of saturated lipids promote domain formation, while those sterols that inhibited tight packing of saturated lipids inhibited domain formation. The ability of some sterols to inhibit domain formation (i.e., act as "anti-cholesterols") should be a valuable tool for examining domain formation and properties in cells.

Insights into the Role of Specific Lipids in the Formation and Delivery of Lipid Microdomains to the Plasma Membrane of Plant Cells

“…The replacement of D 5 -sterols by 9b,19-cyclopropylsterols in membranes from treated plants did not inhibit lipid microdomain formation in the GA, indicating that these compounds remained able to promote microdomains. In this context, biosynthetic precursors of cholesterol, such as 7-dehydrocholesterol or D 7 -cholesterol, have been shown to promote lipid microdomain formation with the same efficiency as cholesterol (Xu and London, 2000;Xu et al, 2001;Keller et al, 2004). In contrast, lanosterol was found to be less efficient.…”

“…In contrast, lanosterol was found to be less efficient. According to Xu and London (2000), those sterols that promote tight packing of lipids also promote domain formation. Our results are therefore consistent with previous studies that gave evidence for 24-methylpollinastanol to be able to order soybean PC bilayers with the same efficiency as sitosterol as assessed by DPH fluorescence polarization or 2 H RMN (Hartmann, 1998).…”

Cholesterol Packing around Lipids with Saturated and Unsaturated Chains: A Simulation Study

“…4 The particular contribution cholesterol makes in the structure of rafts is to facilitate the formation and maintenance of a liquid-ordered (L o ) membrane domain. 5,6 While the majority of experimental studies have involved dipalmitoyl or dimyristoyl phosphatidylcholine (DPPC or DMPC) [7][8][9][10] there are also experimental studies on the effect of cholesterol on palmitoyl-oleyol phosphatidylcholine (POPC). [11][12][13][14][15][16][17][18] Hyslop et al 11 utilized fluorescence depolarization to estimate that cholesterol molecules in a 1:1 POPC:cholesterol bilayer remain separated with a minimum separation distance of ∼10 Å.…”

The effect of cellular cholesterol on membrane-cytoskeleton adhesion

“…Membrane cholesterol is an important factor in determining the physical properties of the lipid bilayer, such as its fluidity (Brulet and McConnell, 1976;Cooper, 1978;Xu and London, 2000) and elasticity (Evans and Needham, 1987;Needham and Nunn, 1990). Specifically, in the case of artificial vesicles, addition of cholesterol increases membrane stiffness (Needham and Nunn, 1990).…”