The Phase Diagram for the Four-Component DSPC/DOPC/POPC/CHOL Mixture

Abstract

When liquid-ordered (Lo) and liquid-disordered (Ld) phases coexist in mixtures of DSPC/DOPC/Chol, phase domains appear as large round domains in giant unilamellar vesicles (GUVs) examined by fluorescence microscopy. However, when liquid-ordered and liquid-disordered phases coexist in DSPC/POPC/Chol mixtures, domain size is too small to be detected by fluorescence microscopy. The phase diagram of the four-component DSPC/DOPC/POPC/Chol mixture allows for the exploration of the transition from macroscopic-to-nanoscopic domains. We have found complex shapes (modulated phase morphology) in a particular region of composition within the liquid-ordered and liquid-disordered coexistence region in DSPC/DOPC/POPC/Chol mixtures. By controlling lipid composition, we see distinct types of modulated liquid-liquid phase morphologies, including linear, irregular, and angular features in GUVs. These studies show that both the size and morphology of membrane rafts can be controlled by adjusting the composition and the type of low-melting lipid in mixtures with high-melting lipid and cholesterol.