A carbon-13 and deuterium nuclear magnetic resonance study of phosphatidylcholine/cholesterol interactions: Characterization of liquid-gel phases

Huang, Tai Huang; Lee, C. W. B.; Gupta, S. K. Das; Blume, Alfred; Griffin, Robert G.

doi:10.1021/bi00211a041

Cited by 171 publications

(204 citation statements)

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“…10,26 The main transition temperature decreases linearly with increasing cholesterol concentration, with a slow decrease until 20 mol % cholesterol and a more rapid decrease beyond this value. This phenomenon has already been described for the DPPC natural analog.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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: ■ Results and Discussionmentioning

confidence: 99%

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

et al. 2016

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“…Detailed phase diagrams of cholesterol in membranes have been constructed by various groups (Lentz et al, 1980;Sankaram & Thompson, 1991;Huang et al, 1993). In the DPPC/cholesterol system, cholesterol has been proposed to be freely distributed in the bilayer at very low concentrations (<5 mol %).…”

Section: Discussionmentioning

confidence: 99%

Membrane Organization at Low Cholesterol Concentrations: A Study Using 7-Nitrobenz-2-oxa-1,3-diazol-4-yl-Labeled Cholesterol

1996

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Cholesterol is most often found distributed nonrandomly in the plane of the bilayer, giving rise to cholesterol-rich and -poor domains. Many of these domains are thought to be crucial for the maintenance of membrane structure and function. However, such well-characterized domains generally occur in the membranes that contain relatively large amounts of cholesterol. Cholesterol organization in membranes containing very low amounts of cholesterol has not been investigated extensively. Recent evidence from differential-scanning calorimetric studies suggests that cholesterol may not form uniform monodisperse solutions, as assumed earlier, in the membranes even at very low concentrations. Fluorescent cholesterol analogues, when chosen carefully, offer a powerful approach for studying the distribution and organization of cholesterol in membranes at low concentrations. In this paper, we have studied the organization of cholesterol in membranes at very low concentrations (up to 5 mol % of the total lipid) using a fluorescent cholesterol analogue (NBD-cholesterol) which is labeled with the 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group at the flexible acyl chain, without any alteration in the structural features necessary for proper membrane incorporation. Our results show that NBD-cholesterol exhibits local organization even at very low concentrations. This is consistent with the recently suggested model of cholesterol organization in membranes at low concentrations, involving the formation of transbilayer, tail-to-tail dimers The fluid mosaic model for biological membranes defines the membrane as an oriented, two-dimensional, viscous solution of proteins and lipids in instantaneous thermodynamic equilibrium (Singer & Nicolson, 1972). Although the basic tenets of this model have stood the test of time, one of its implicit assumptions, that the lipid molecules merely provide the milieu for the membrane proteins and that they are distributed uniformly throughout the bilayer, has been found to be not quite true. In fact, current evidence points out that both transverse and lateral regionalization, which can be described in terms of micro-and macrodomains, are common features of many biological membranes (Curtain et al., 1988;Edidin, 1992;Tocanne, 1992;Glaser, 1993;Jacobson et al., 1995).Cholesterol is one of the membrane components that is found, more often than not, distributed nonrandomly in structural and kinetic domains or pools in both biological and model membranes (Yeagle, 1985;Gennis, 1989;Schroeder et al., 1991;Liscum & Underwood, 1995). The reason for this lies in the rather unusual chemical structure of cholesterol that can by no means be considered a representative component of the "bulk" membrane (see Figure 1). The unusual shape of cholesterol also causes a phase separation in membranes at relatively high concentrations, resulting in the formation of cholesterol-rich and -poor domains that are structurally and compositionally so distinct that they can be observed histochemically and isolated physical...

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“…Lipid bilayers containing cholesterol may also exhibit phase separation into cholesterol-rich (liquid-ordered) and cholesterol-poor (liquid disordered) domains with the increase of cholesterol content [11,[19][20][21][22][23][24], although the molecular organization of such cholesterol-containing bilayers is still a matter of debate, as is the significance of the structures like lipid rafts and hexagonal superlattices [25][26][27][28][29]. With the increasing fraction of cholesterol, the BLM became more stable at the beginning, and the threshold voltage of bilayer breakdown (rupture) was initially increased.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…However, while the addition of cholesterol to pure phosphatidylcholine BLMs reduced the incidence of pore formation, ASA accelerated the creation of metastable single pores and facilitated membrane rupture. Under conditions of our experiment, the BLMs composed of pure phosphatidylcholine are in the gel state, and their enrichment in cholesterol has a stabilizing effect due to clustering of the sterol within the phosphatidylcholine lipid core [11][12][13]18,21,23,24,[30][31][32][33][34]. ASA is known to spontaneously decompose (hydrolyze) into acetate and SA, although this process is relatively slow and takes 5-6 hours [35].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Effect of acetylsalicylic acid on the current–voltage characteristics of planar lipid membranes

Watała

Drapeza²,

Loban³

et al. 2009

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. contributed to the formation of metastable single pores, which facilitated ASA diffusion through a bilayer. Our data point out that ASA transport across the lipid bilayer takes place predominantly via the process of passive diffusion. In conclusion, the effects of ASA on lipid bilayer stability may contribute to drug transport through membrane lipid bilayers. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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A carbon-13 and deuterium nuclear magnetic resonance study of phosphatidylcholine/cholesterol interactions: Characterization of liquid-gel phases

Cited by 171 publications

References 49 publications

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

Membrane Organization at Low Cholesterol Concentrations: A Study Using 7-Nitrobenz-2-oxa-1,3-diazol-4-yl-Labeled Cholesterol

Effect of acetylsalicylic acid on the current–voltage characteristics of planar lipid membranes

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