Kinetics of soluble lipid monomer diffusion between vesicles

Nichols, J. Wylie; Pagano, Richard E.

doi:10.1021/bi00513a012

Cited by 252 publications

(197 citation statements)

References 25 publications

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“…Concentration dependent self-quenching of the NBD group is quite well-characterized (Nichols & Pagano, 1981;McIntyre et al, 1993;Prieto et al, 1994) and constitutes the basis of a large number of assays in membrane biology, such as the phase separation of lipids (Hoekstra, 1982;Wiener et al, 1985), phospholipid transfer between mixed micelles (Nichols, 1988), and phospholipase A 2 activity (Meyuhs et al, 1992). However, what we observe in this paper is not nonspecific quenching of fluorescence.…”

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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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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“…[17][18][19][20][21][22]. and with lipids bearing fluorescent dyes (e.g., [23][24][25][26][27][28][29][30]. While one might argue that inserting lipids into membranes is better achieved using soluble lipid transfer proteins.…”

Section: Ii-a Value As An Experimental Toolmentioning

confidence: 99%

“…The mechanism by which spontaneous lipid transfer occurs between membranes has been investigated in many independent laboratories [23,26,57,66,[110][111][112][113][114][132][133][134][135]. In the vast majority of cases, it has been concluded that the transfer event is a first-order process in which the rate-limiting step is desorption of lipid molecules from the donor membrane surface followed by rapid diffusion through the aqueous phase to an acceptor membrane (Fig.…”

Section: What Is the Mechanism Of Spontaneous Lipid Transfer? Iv-mentioning

confidence: 99%

“…However, as was pointed out above, the majority of experimental data reported prior to 1988 argued against such a mechanism of lipid transfer (e.g., Refs. 23,26,57,66,[110][111][112][113][114][132][133][134][135]. Then, two different laboratories both reported increased spontaneous lipid transfer rates attributable to transient collisions between donor and acceptor surfaces [96][97][98][107][108][109].…”

Section: Iv-b Transient Apposition Of Hydrated Membrane Surfacesmentioning

confidence: 99%

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Spontaneous lipid transfer between organized lipid assemblies

Brown

1992

Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes

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“…Previous studies have demonstrated that, when cells or lipid vesicles are incubated with liposomes containing another short-chain phospholipid, 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)-aminocaproyl phosphatidylcholine, the fluorescent lipid spontaneously transfers between membranes (47). The mechanism for this transfer has been demonstrated to be diffusion of soluble fluorescent lipid monomers (48). It is very likely that the exchange of the even more polar oxidized phospholipids under investigation between the donor particles and cells is driven by the same process.…”

Section: Discussionmentioning

confidence: 99%

Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells

Moumtzi

Trenker

Flicker

et al. 2007

Journal of Lipid Research

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Lipid oxidation is now thought to be an initiating and sustaining event in atherogenesis. Oxidatively fragmented phospholipids, namely 1-palmitoyl-2-glutaroylsn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), present in minimally modified LDL and atherosclerotic lesions, have been reported to elicit a wide range of pathophysiological responses in the cells of the vascular wall. Nevertheless, the question of their potential sites of action and their primary molecular targets remains open. To address this issue, a series of fluorescently labeled analogs, which differ with regard to structure and binding site of the fluorophore, were synthesized and used as tools for studying the uptake, intracellular stability, and distribution of PGPC and POVPC in vascular smooth muscle cells (VSMCs). We demonstrate that in accordance with their lysophospholipid-like structure, these highly similar molecules transferred rapidly either from aqueous phospholipid dispersions or preloaded native LDL into VSMCs, producing disparate fluorescence patterns irrespective of the attached fluorophore. PGPC derivatives were translocated to the lysosomes. In sharp contrast, POVPC analogs were initially captured in the plasma membrane, most likely in consequence of the formation of covalent adducts with free amino and sulfhydryl groups of proteins and phospholipids.

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Kinetics of soluble lipid monomer diffusion between vesicles

Cited by 252 publications

References 25 publications

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

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

Spontaneous lipid transfer between organized lipid assemblies

Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells

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