Surface Occupancy Plays a Major Role in Cholesterol’s Condensing Effect

Krause, Martin R.; Türkyilmaz, Serhan; Regen, Steven L.

doi:10.1021/la402263w

Cited by 8 publications

(10 citation statements)

References 24 publications

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“…Cholesterol is a flat molecule maximizing the hydrophobic forces in model phospholipid membranes . Cholesterol hereby acts as a fluidity buffer, and this leveling effect leads to a liquid-ordered membrane phase .…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: ■ Introductionmentioning

confidence: 99%

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Vesicle Origami and the Influence of Cholesterol on Lipid Packing

et al. 2016

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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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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

et al. 2016

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“…Chol has a pronounced effect on the thermotropic phase behavior and organization of DPPC bilayers ( 23 , 24 ). The high stability of DPPC liposomes containing Chol has been demonstrated and explained by the formation of stronger condensed binary complexes in these lipid layers ( 25 ).…”

Section: Resultsmentioning

confidence: 99%

The Vacuolar Pathway in Macrophages Plays a Major Role in Antigen Cross-Presentation Induced by the Pore-Forming Protein Sticholysin II Encapsulated Into Liposomes

et al. 2018

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Cross-presentation is an important mechanism for the differentiation of effector cytotoxic T lymphocytes (CTL) from naïve CD8+ T-cells, a key response for the clearance of intracellular pathogens and tumors. The liposomal co-encapsulation of the pore-forming protein sticholysin II (StII) with ovalbumin (OVA) (Lp/OVA/StII) induces a powerful OVA-specific CTL activation and an anti-tumor response in vivo. However, the pathway through which the StII contained in this preparation is able to induce antigen cross-presentation and the type of professional antigen presenting cells (APCs) involved have not been elucidated. Here, the ability of mouse bone marrow-derived dendritic cells (BM-DCs) and macrophages (BM-MΦs) stimulated with Lp/OVA/StII to activate SIINFEKL-specific B3Z CD8+ T cells was evaluated in the presence of selected inhibitors. BM-MΦs, but not BM-DCs were able to induce SIINFEKL-specific B3Z CD8+ T cell activation upon stimulation with Lp/OVA/StII. The cross-presentation of OVA was markedly decreased by the lysosome protease inhibitors, leupeptin and cathepsin general inhibitor, while it was unaffected by the proteasome inhibitor epoxomicin. This process was also significantly reduced by phagocytosis and Golgi apparatus function inhibitors, cytochalasin D and brefeldin A, respectively. These results are consistent with the concept that BM-MΦs internalize these liposomes through a phagocytic mechanism resulting in the cross-presentation of the encapsulated OVA by the vacuolar pathway. The contribution of macrophages to the CTL response induced by Lp/OVA/StII in vivo was determined by depleting macrophages with clodronate-containing liposomes. CTL induction was almost completely abrogated in mice depleted of macrophages, demonstrating the relevance of these APCs in the antigen cross-presentation induced by this formulation.

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“…6. The cholesterol is seemed to incorporate in a lipid bilayer membrane such as liposome, remove the membrane interdigitation, and induce a liquid-ordered phase [27,28]. It is suggested that a high amount of cholesterol orientates in the acyl chain of the C 12 -GLG-C 12 membrane more than liposomes due to the spacer of C 12 -GLG-C 12 consisting two glutamic acids and a lysine is larger than that of phosphatidylcholine.…”

Section: Discussionmentioning

confidence: 99%

Preparation and Physicochemical Properties of Lauroyl‐Glutamyl‐Lysil‐Lauroyl‐Glutamate Vesicles

Fujii

Fujisaki

Fukuda³

et al. 2017

J Surfact & Detergents

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We investigate the compositions of vesicle formulation by assembling phase diagrams of the ternary components of lauroyl‐glutamyl‐lysil‐lauroyl‐glutamate (C12‐GLG‐C12) peptide‐based gemini‐type amphiphile/citric acid/water using visual and microscopic observations. To clarify interactions between C12‐GLG‐C12 and citric acid, turbidity and zeta potential of the mixtures were investigated. To improve the stability of metastable vesicles, appropriate additives were examined by measuring particle size and zeta potential, visual observation and transmission electron microscopy. The turbidity increased and the absolute value of zeta potential decreased with increasing citric acid concentration in C12‐GLG‐C12/citric acid solutions. Then, a metastable γ region having vesicles was formed. The stability of vesicles increased with increasing cholesterol concentrations. This result suggests that a coacervation has occurred due to the effective cross‐sectional area decreasing with increasing C12‐GLG‐C12 hydrophobicity, which was derived from inhibition of the carboxyl group dissociation. Furthermore, we hypothesized that the orientation of cholesterol between vesicle membranes is a contributing factor to improve the vesicle stability. From transmission electron microscopic observations, it was made clear that the vesicles consisting of cholesterol and C12‐GLG‐C12 at a molar ratio of 2:1 showed multilayered structures. The vesicles consisting of C12‐GLG‐C12, cholesterol and citric acid are expected to be used as transdermal drug delivery system carriers, as they can be easily prepared using biocompatible compounds without the use of organic solvents such as chloroform.

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Surface Occupancy Plays a Major Role in Cholesterol’s Condensing Effect

Cited by 8 publications

References 24 publications

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

The Vacuolar Pathway in Macrophages Plays a Major Role in Antigen Cross-Presentation Induced by the Pore-Forming Protein Sticholysin II Encapsulated Into Liposomes

Preparation and Physicochemical Properties of Lauroyl‐Glutamyl‐Lysil‐Lauroyl‐Glutamate Vesicles

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