Effects of the replacement of a double bond by a cyclopropane ring in phosphatidylethanolamines: a deuterium NMR study of phase transitions and molecular organization

Perly, Bruno; Smith, Ian C. P.; Jarrell, Harold C.

doi:10.1021/bi00325a038

Cited by 80 publications

(72 citation statements)

References 31 publications

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“…At 30 • C, the |SCH| values for the fluid fraction of the clinical-type LSE sample were determined to be 0.2 to 0.25 for the first acyl-chain carbons and decrease along the acyl chain and finally reach values close to zero for ω CH3. The |SCH| profile closely resembles previously measured SCH profiles of saturated acyl chains in the L α(d) phase (29,47,48) in model phospholipid systems with simple composition. The decrease of |SCH| from the acyl-chain carbons near the glycerol backbone to the carbons at the bilayer center relates to the different probabilities for dihedral rotations along the acyl chains.…”

Section: Resultssupporting

confidence: 83%

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson

Grey

Larsson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The lipid-protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of 1 H-13 C solid-state nuclear magnetic spectroscopy, small-and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, L α(o) , at physiological temperatures. This L α(o) phase gradually changes into a liquid-disordered lamellar phase, L α(d) , when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one L α(d) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes |S CH | from the liquiddisordered and -ordered lamellar phases and assign them to specific C-H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological selfassembly compositions for treatment of pathological states such as respiratory distress syndrome.T he air-alveoli interface of human lungs consists of ∼100 m 2 of surface area covered by a 1-to 2-µm-thick film rich in lipids, generally referred to as lung surfactant (LS) (1, 2). The alveolar interfacial film has several important functions, including stabilizing the interface, allowing for area expansions and controlling diffusional transport (3-7). These functions strongly rely on the self-assembly structure, as well as on the mechanical, barrier, and surface properties of the dynamic LS interfacial layer, which in turn depend on its chemical composition and external conditions in terms of compression, hydration, and so on. The main components of LS are phospholipids, cholesterol, and the so-called surfactant proteins representing ∼80, 10, and 10 wt %, respectively (2).Deficiency of LS in the alveoli, or an imbalance of its chemical composition, induces a number of pathological conditions (8). For instance, neonatal respiratory distress syndrome affects prematurely born infants when LS is not yet matured or is completely lacking; this deficiency may be lethal if left untreated. In these cases, the most common treatment is intratracheal administration of an exogenous LS into the lungs (9). In case of acute respiratory distress syndrome the mortality is 35 to 45% (10) and an effective treatment is clearly lacking (8). An accurate characterization of the molecular structure and dynamics of endogenous an...

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Section: Resultssupporting

confidence: 83%

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson

Grey

Larsson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…[14,34] In Sim2 and Sim3, the average area per lipid is slightly larger than experimental values, whereas the membrane thickness is thinner. We also found that the order parameters |S CD | of lipids with d min > 18 Å in Sim4 were closer to experimental values, [35][36][37] compared to those in Sim2 and Sim3 (see Supporting Information, Fig. S4).…”

Section: Consistency With Other Structural Parameters Of Lipid Bilayerssupporting

confidence: 73%

Analysis of lipid surface area in protein–membrane systems combining voronoi tessellation and monte carlo integration methods

2011

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All-atom molecular dynamics (MD) simulation has become a powerful research tool to investigate structural and dynamical properties of biological membranes and membrane proteins. The lipid structures of simple membrane systems in recent MD simulations are in good agreement with those obtained by experiments. However, for protein-membrane systems, the complexity of protein-lipid interactions makes investigation of lipid structure difficult. Although the area per lipid is one of the essential structural properties in membrane systems, the area in protein-membrane systems cannot be computed easily by conventional approaches like the Voronoi tessellation method. To overcome this limitation, we propose a new method combining the two-dimensional Voronoi tessellation and Monte Carlo integration methods. This approach computes individual surface areas of lipid molecules not only in bulk lipids but also in proximity to membrane proteins. We apply the method to all-atom MD trajectories of the sarcoplasmic reticulum Ca(2+)-pump and the SecY protein-conducting channel. The calculated lipid surface area is in agreement with experimental values and consistent with other structural parameters of lipid bilayers. We also observe changes in the average area per lipid induced by the conformational transition of the SecY channel. Our method is particularly useful for examining equilibration of lipids around membrane proteins and for analyzing the time course of protein-lipid interactions.

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“…1 shows the raw data for the apparent specific volumes υ of mixtures of cholesterol with several different lipids as a function of cholesterol mole fraction x. For most of the samples, the pure lipid bilayers were in the fluid Lα phase, T > T M , where the chain melting temperature T M is 41.4 °C for DPPC (Nagle and Wilkinson, 1978), 24.0 °C for DMPC (Nagle and Wilkinson, 1978), 39°C for BSM (McIntosh et al, 1992), −5 °C for POPC (Perly et al, 1985) and −15.5 °C for DOPC (Webb et al, 1993). Employing the convention that the temperature will be placed in parentheses after the acronym for the lipid, these samples were DOPC(30), POPC(30), DPPC(50), DMPC(30) and BSM(45).…”

Section: Discussionmentioning

confidence: 99%

Partial molecular volumes of lipids and cholesterol

Greenwood

Tristram-Nagle

Nagle

2006

Chemistry and Physics of Lipids

212

193

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Volumetric measurements are reported for fully hydrated lipid/cholesterol bilayer mixtures using the neutral flotation method. Apparent specific volume data were obtained with the lipids DOPC, POPC and DMPC at T = 30 °C, DPPC at 50 °C, and brain sphingomyelin (BSM) at 45 and 24 °C for mole fractions of cholesterol x from 0 to 0.5. Unlike previous cholesterol mixture studies, we converted our raw data to partial molecular volume V L of the lipid and V C of the cholesterol. The partial molecular volumes were constant for POPC and DOPC as x was varied, but had sharp breaks for the other lipids at values of x C near 0.25 ± 0.05. Results for x < x C clearly exhibit the condensation effect of cholesterol on DPPC, DMPC and BSM when measured at temperatures above their main transition temperatures T M . The break points at x C are compared to phase diagrams in the literature. For x > x C the values of the partial molecular volumes of cholesterol clustered near 630 ± 10 Å 3 in all the lipids when measured for T > T M ; we suggest that this is the most appropriate measure of the bare volume of cholesterol in lipid bilayers.

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Effects of the replacement of a double bond by a cyclopropane ring in phosphatidylethanolamines: a deuterium NMR study of phase transitions and molecular organization

Cited by 80 publications

References 31 publications

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Analysis of lipid surface area in protein–membrane systems combining voronoi tessellation and monte carlo integration methods

Partial molecular volumes of lipids and cholesterol

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