Abstract
Phosphoinositides (PIPs) have been shown to mediate a large variety of membrane trafficking events. Phosphatidylinositol (PI) is involved in these signaling events since it is a precursor for PIPs. In addition to this role, we hypothesize that the interaction of PI with PIPs affects the lateral distribution of PIPs and hence the spatial organization of the respective signaling event. The spatial organization of PI/PIPs is expected to be further modulated by the presence of cholesterol. To explore these questions, we studied the effect of PI on PIP domain formation in the absence/presence of cholesterol. While binary mixtures of PC/PI or PC/PIP2 did not reveal any macroscopically discernable domains, we observed in the presence of cholesterol the formation of PI and PI(4,5)P2 enriched domains. For cholesterol derivatives such as cholestenone or cholesterylester, we did not observe the formation of domains, indicating that the cholesterol hydroxyl group is an important factor for the observed interaction between the sterol and the lipid. We extended our studies to ternary mixtures of PC/PI/PI(4,5)P2, which showed also in the absence of cholesterol domain formation for physiologically relevant concentrations of the anionic lipids. We believe that the presence of PI “dilutes” the high negative charge found at the PI(4,5)P2 headgroup, allowing PI and PI(4,5)P2 to co-localize in domains. Using fluorescence microscopy measurements of GUVs and monolayers at the air/water interface, we extended this study further and investigated the effect of cholesterol on the morphology of these ternary lipid systems.
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