Vesicle Origami and the Influence of Cholesterol on Lipid Packing

Abstract

ABSTRACT:The artificial phospholipid Pad-PC-Pad was analyzed in 2D (monolayers at the air/water interface) and 3D (aqueous lipid dispersions) systems. In the gel phase, the two leaflets of a Pad-PC-Pad bilayer interdigitate completely, and the hydrophobic bilayer region has a thickness comparable to the length of a single phospholipid acyl chain. This leads to a stiff membrane with no spontaneous curvature. Forced into a vesicular structure, Pad-PC-Pad has faceted geometry, and in its extreme form, tetrahedral vesicles were found as predicted a decade ago. Above the main transition temperature, a noninterdigitated L α phase with fluid chains has been observed. The addition of cholesterol leads to a slight decrease of the main transition temperature and a gradual decrease in the transition enthalpy until the transition vanishes at 40 mol % cholesterol in the mixture. Additionally, cholesterol pulls the chains apart, and a noninterdigitated gel phase is observed. In monolayers, cholesterol has an ordering effect on liquid-expanded phases and disorders condensed phases. The wavenumbers of the methylene stretching vibration indicate the formation of a liquid-ordered phase in mixtures with 40 mol % cholesterol. ■ INTRODUCTIONVesicle origami or the guided self-assembly of a soft matter liposome may lead to materials with unprecedented properties. However, imposing a specific form on a liposome remains a formidable challenge. To achieve this goal, more fundamental insight into the forces determining the local curvature in membranes is needed.Here, we analyze the effects of membrane interdigitation and the deinterdigitating effect of cholesterol on monolayers and bilayers. Moreover, the liquid-ordered phase is characterized in unprecedented clarity.Cholesterol is a flat molecule maximizing the hydrophobic forces in model phospholipid membranes. 1 Cholesterol hereby acts as a fluidity buffer, 2 and this leveling effect leads to a liquidordered membrane phase. 3 In a nonideal mixture of low-and high-melting glycerophospholipids, cholesterol associates preferentially with the high-melting, saturated lipids. 4 Cholesterol and the glycerophospholipids interact strongly but transiently 5 via (i) hydrogen bonds between the hydroxy group of cholesterol and the phospholipid phosphodiester, 6 (ii) hydrogen bonds among the hydroxy group of cholesterol, water, and the sn-1 carbonyl moiety of the phospholipid, 7 (iii) van der Waals hydrophobic forces between the planar cholesterol ring system and the sn-1 chain of the phospholipid, 8 and, most importantly, (iv) van der Waals forces between the fatty acyl chains and the cholesterol side chain. 9 The interactions are strongly dependent on the type of phospholipid headgroup and lipid tail saturation 10 and may lead to a positioning of cholesterol in the middle of the bilayer membrane in the presence of polyunsaturated phospholipids. 11 Here, we discuss the effect of cholesterol on monolayers and bilayers formed by artificial 1,3-diamidophospholipid Pad-PCPad (structures in Figure 1). B...

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