Dipole Modifiers Regulate Lipid Lateral Heterogeneity in Model Membranes

Abstract

In this study we report on experimental observations of giant unilamellar liposomes composed of ternary mixtures of cholesterol (Chol), phospholipids with relatively low Tmelt (DOPC, POPC, or DPoPC) and high Tmelt (sphingomyelin (SM), or tetramyristoyl cardiolipin (TMCL)) and their phase behaviors in the presence and absence of dipole modifiers. It was shown that the ratios of liposomes exhibiting noticeable phase separation decrease in the series POPC, DOPC, DPoPC regardless of any high-Tmelt lipid. Substitution of SM for TMCL led to increased lipid phase segregation. Taking into account the fact that the first and second cases corresponded to a reduction in the thickness of the lipid domains enriched in low- and high-Tmelt lipids, respectively, our findings indicate that the phase behavior depends on thickness mismatch between the ordered and disordered domains. The dipole modifiers, flavonoids and styrylpyridinium dyes, reduced the phase segregation of membranes composed of SM, Chol, and POPC (or DOPC). The other ternary lipid mixtures tested were not affected by the addition of dipole modifiers. It is suggested that dipole modifiers address the hydrophobic mismatch through fluidization of the ordered and disordered domains. The ability of a modifier to partition into the membrane and fluidize the domains was dictated by the hydrophobicity of modifier molecules, their geometric shape, and the packing density of domain-forming lipids. Phloretin, RH 421, and RH 237 proved the most potent among all the modifiers examined.

Interaction of membrane palmitoylated protein-1 with model lipid membranes

“…An example of such lipid mixtures is one with equimolar amounts of dioleoylphosphatidylcholine (DOPC), sphingomyelin (SM), and cholesterol (Chol). This ternary lipid mixture has been widely studied by many techniques for its ability to form two immiscible liquid domains containing more ordered domains that consist mainly of SM/ Chol surrounded by domains in a more liquid state (Edidin 2003;Goñi et al 2008;Fritzsching et al 2013;Maté et al 2014;Efimova and Ostroumova 2017;Bhojoo et al 2018;Henry et al 2018;Parkkila et al 2018;Paulowski et al 2018). Significantly, we have recently shown that MPP1 interacts with lipid mono-and bilayers in artificial systems composed of this ternary lipid mixture (DOPC/SM/Chol) (Elderdfi et al 2017).…”