Lateral Diffusion Rates of Lipid, Water, and a Hydrophobic Drug in a Multilamellar Liposome

Gaede, Holly C.; Gawrisch, Klaus

doi:10.1016/s0006-3495(03)74603-7

Cited by 154 publications

(155 citation statements)

References 30 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…For comparison, the diffusion rate of water molecules in water at ambient temperature is about three orders of magnitude higher (2.1 10 -9 m 2 s -1 , (Price et al 1999)). Even the lateral diffusion rate of POPC in bilayers (8 × 10 -12 m 2 s -1 , (Gaede and Gawrisch 2003)) is significantly higher. Therefore it is likely that water molecules pass through the hydrophobic core in a fraction of a microsecond and, consequently, the water concentration in the core of the bilayer is lower than one water molecule per lipid, in agreement with experimental observations.…”

Section: Discussionmentioning

confidence: 92%

Hydration of POPC bilayers studied by 1H-PFG-MAS-NOESY and neutron diffraction

et al. 2007

Self Cite

View full text Add to dashboard Cite

The stability of lipid bilayers is ultimately linked to the hydrophobic effect and the properties of water of hydration. Magic angle spinning (MAS) nuclear Overhauser enhancement spectroscopy (NOESY) with application of pulsed magnetic field gradients (PFG) was used to study the interaction of water with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers in the fluid phase. NOESY cross-relaxation between water and polar groups of lipids, but also with methylene resonances of hydrophobic hydrocarbon chains, has been observed previously. This observation led to speculations that substantial amounts of water may reside in the hydrophobic core of bilayers. Here, the results of a quantitative analysis of cross-relaxation in a POPC/water mixture are reported. Coherences were selected via application of pulsed magnetic field gradients. This technique shortens acquisition times of NOESY spectra to 20 minutes and reduces t 1 -spectral noise, enabling detection of weak crosspeaks, like those between water and lipids, with higher precision than with non-gradient NOESY methods. The analysis showed that water molecules interact almost exclusively with sites of the lipid-water interface, including choline-, phosphate-, glycerol-, and carbonyl groups. The lifetime of lipid-water associations is rather short, on the order of 100 ps, at least one order of magnitude shorter than the lifetime of lipid-lipid associations. The distribution of water molecules over the lipid bilayer was measured at identical water content by neutron diffraction. Water molecules penetrate deep into the interfacial region of bilayers but water concentration in the hydrophobic core is below the detection limit of one water molecule per lipid, in excellent agreement with the cross-relaxation data.

show abstract

Section: Discussionmentioning

confidence: 92%

Hydration of POPC bilayers studied by 1H-PFG-MAS-NOESY and neutron diffraction

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lipid diffusion experiments by 1 H MAS NMR with application of pulsed magnetic field gradients were performed at a spinning frequency of 10 kHz, as described previously 25 and recapped briefly in the Supplementary Methods online.…”

Section: Methodsmentioning

confidence: 99%

“…For samples with coexisting membrane domains, the centerband of the 1 H MAS NMR spectrum is dominated by narrow peaks from the l d phase, whereas broad components from the ordered phases are markedly pronounced in the sideband region of the spectrum. Moreover, 1 H MAS NMR with application of pulsed magnetic field gradients enables measurement of lipid diffusion rates in membranes 25 and of fluid domain sizes 20 . Here we apply these techniques to test the hypothesis that ordered lipids exist in the envelope of the influenza virus.…”

mentioning

confidence: 99%

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

Polozov¹,

Bezrukov²,

Gawrisch³

et al. 2008

Nat Chem Biol

Self Cite

211

159

View full text Add to dashboard Cite

Using linewidth and spinning sideband intensities of lipid hydrocarbon chain resonances in proton magic angle spinning NMR spectra, we detected the temperature-dependent phase state of naturally occurring lipids of intact influenza virus without exogenous probes. Increasingly, below 41 1C ordered and disordered lipid domains coexisted for the viral envelope and extracts thereof. At 22 1C much lipid was in a gel phase, the fraction of which reversibly increased with cholesterol depletion. Diffusion measurements and fluorescence microscopy independently confirmed the existence of gel-phase domains. Thus the existence of ordered regions of lipids in biological membranes is now demonstrated. Above the physiological temperatures of influenza infection, the physical properties of viral envelope lipids, regardless of protein content, were indistinguishable from those of the disordered fraction. Viral fusion appears to be uncorrelated to ordered lipid content. Lipid ordering may contribute to viral stability at lower temperatures, which has recently been found to be critical for airborne transmission.Membranes of most enveloped viruses form by budding out from the plasma membranes of their host cells a highly select subset of plasma membrane components. In general, the selected membrane proteins are coded by the viral genome, whereas lipids are recruited from host membranes; however, the lipid composition of the viral envelope differs from that of the host membrane 1,2 and from other budding viruses 3 . The envelope of influenza contains higher amounts of both cholesterol 1 and glycosphingolipids 4 -lipids known to partition into the liquid ordered (l o ) phase. The l o phase is characterized by extended hydrocarbon chains having a reduced gauche-trans isomerization compared with those of the liquid disordered (l d ) phase, but having a similar rotational and translational mobility 5 . Liquid ordered phases are thought to be at the core of lipid rafts 6 , which are defined as transient membrane microdomains that are enriched in sphingolipids and cholesterol (1) 7 -a hypothesis that has generated much debate 8,9 .The influenza virus has played a pivotal role in the development of the raft hypothesis, starting with early studies that inferred ordered domains using spin probes 10-12 and fluorescence 13,14 and that suggested that an ordered lipid domain is selected in toto as the envelope during budding from the plasma membrane 15 . These lipids are either selected at the time of budding or pre-selected as the 'pre-envelope' suggested by clusters of the viral envelope protein hemagglutinin seen in immunoelectron microscopy 16 .Although detection of virus-sized domains of lipids (B100-nm diameter) is below the limit of resolution of fluorescent microscopy, large micrometer-sized membrane domains are reliably detected [17][18][19] . Recently, proton magic angle spinning NMR ( 1 H MAS NMR) has been used to determine the phase diagram of the same lipid compositions used to study large membrane domains in lipid bilayers and othe...

show abstract

“…[92][93][94] Due to the anisotropic molecular reorientation of these liquid crystalline (LC) systems, significant dipolar coupling remains, leading to broad lines and short relaxation times. However dipolar coupling can be reduced through the use of MAS.…”

Section: Diffusion In Zeolites Nanoparticles and Liquid Crystalsmentioning

confidence: 99%