Exclusion of poly(ethylene glycol) from liposome surfaces

Arnold, Klaus; Zschoernig, Olaf; Barthel, D; Herold, W.

doi:10.1016/0005-2736(90)90278-v

Cited by 114 publications

(69 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If we consider two negatively charged membranes embedded in a polyelectrolyte solution, ions tend to accumulate into the interlamellar space to shield the electrostatic repulsion between membranes, promoting the exclusion of polymer (salting-out mechanism). As a consequence of the electro-osmotic release of polymer, negatively charged membranes feel each other at longer distances than neutral membranes, as hypothesized by some authors on the basis of experimental evidence 29,30 and proved by us by electrostatic modelling and MD simulations. 8 33,34 Calcium ions trigger this event by constricting the lipid headgroups in a partially dehydrated state.…”

Section: Discussionmentioning

confidence: 62%

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Pannuzzo

Jong

Raudino

et al. 2014

The Journal of Chemical Physics

View full text Add to dashboard Cite

Anomalous viscosity effect in the early stages of the ion-assisted adhesion/fusion event between lipid bilayers: A theoretical and computational study J. Chem. Phys. 138, 234901 (2013) We report on the mechanism of membrane fusion mediated by polyethylene glycol (PEG) and Ca 2+ by means of a coarse-grained molecular dynamics simulation approach. Our data provide a detailed view on the role of cations and polymer in modulating the interaction between negatively charged apposed membranes. The PEG chains cause a reduction of the inter-lamellar distance and cause an increase in concentration of divalent cations. When thermally driven fluctuations bring the membranes at close contact, a switch from cis to trans Ca 2+ -lipid complexes stabilizes a focal contact acting as a nucleation site for further expansion of the adhesion region. Flipping of lipid tails induces subsequent stalk formation. Together, our results provide a molecular explanation for the synergistic effect of Ca 2+ and PEG on membrane fusion. © 2014 AIP Publishing LLC.

show abstract

Section: Discussionmentioning

confidence: 62%

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Pannuzzo

Jong

Raudino

et al. 2014

The Journal of Chemical Physics

View full text Add to dashboard Cite

show abstract

“…PEG-induced fusion of model membranes has been well studied (36,37). It is hypothesized that PEG can force very close contact between vesicle membranes by lowering the activity of water adjacent to the membrane (38). In addition, PEG can dehydrate the lipid bilayer, leading to the formation of nonlamellar structures, raising the gel-to-fluid phase transition temperature (39,40), and enhancing membrane permeability (41).…”

Section: Discussionmentioning

confidence: 99%

Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Förster resonance energy transfer imaging

Chen

Kim

et al. 2008

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

362

290

View full text Add to dashboard Cite

It is generally assumed that polymeric micelles, upon administration into the blood stream, carry drug molecules until they are taken up into cells followed by intracellular release. The current work revisits this conventional wisdom. The study using duallabeled micelles containing fluorescently labeled copolymers and hydrophobic fluorescent probes entrapped in the polymeric micelle core showed that cellular uptake of hydrophobic probes was much faster than that of labeled copolymers. This result implies that the hydrophobic probes in the core are released from micelles in the extracellular space. Fö rster resonance energy transfer (FRET) imaging and spectroscopy were used to monitor this process in real time. A FRET pair, DiIC 18(3) and DiOC18(3), was loaded into monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) micelles. By monitoring the FRET efficiency, release of the core-loaded probes to model membranes was demonstrated. During administration of polymeric micelles to tumor cells, a decrease of FRET was observed both on the cell membrane and inside of cells, indicating the release of core-loaded probes to the cell membrane before internalization. The decrease of FRET on the plasma membrane was also observed during administration of paclitaxel-loaded micelles. Taken together, our results suggest a membrane-mediated pathway for cellular uptake of hydrophobic molecules preloaded in polymeric micelles. The plasma membrane provides a temporal residence for micelle-released hydrophobic molecules before their delivery to target intracellular destinations. A putative role of the PEG shell in the molecular transport from micelle to membrane is discussed. Block copolymer micelles (1-4) have attracted growing interest as carriers to deliver drugs including antitumor reagents to the target site via the enhanced permeability and retention effect (5). Hydrophobic molecules, such as paclitaxel (PTX), can be incorporated into the core of polymeric micelles by physical entrapment. The core composed of hydrophobic chains is expected to regulate the retention and the release of loaded drug molecules on an appropriate time scale (6-8). With micelle-based drug formulations reaching clinical trials (9, 10), the impetus for understanding the pathways involved in micellar drug delivery starts to emerge. It is thought that intact polymeric micelles are taken into cells, followed by intracellular release of drug molecules (8). Kabanov's group (11) reported that pluronic copolymer micelles could be internalized by an endocytic pathway and increase drug absorption by inhibition of P-glycoprotein drug efflux system in cancer cells. Allen et al. (12) suggested that poly(ethylene oxide)-poly(-caprolactone) (PEO-PCL) micelles enter PC12 cells via endocytosis. To directly monitor the micelles, Luo et al. (13) and Savic et al. (14) chemically conjugated a rhodamine molecule to the end of the PCL block and investigated the internalization of PEO-PCL micelles into P19 and PC12 cells. In their study, micelles were reported to en...

show abstract

“…(Q) when ubiquinol-2 is the reducing substrate. It has been reported that polymeric viscosogens do not interfere with short-range diffusion of small molecules (Phillips et al, 1977) and that PEG is excluded from liposome (and presumably membrane) surfaces (Arnold et al, 1990 (Figure 5), the value of the diffusion-limited component can be determined and the collisional efficiency calculated as the fraction of collisions-that result in a reaction (i.e. the ratio of the diffusion-controlled component of kmin (c) to the collisional frequency calculated from the diffusion coefficient).…”

Section: Effect Of Medium Viscositymentioning

confidence: 99%

Steady-state kinetics of ubiquinol-cytochrome c reductase in bovine heart submitochondrial particles: diffusional effects

Fato

Cavazzoni

Castelluccio

et al. 1993

Biochemical Journal

View full text Add to dashboard Cite

In an attempt to establish the relative importance of diffusional and chemical control in the reactivity of the two substrates, ubiquinol and cytochrome c, we have undertaken an extensive characterization of the steady-state kinetics of ubiquinol-cytochrome c reductase (EC 1.10.2.2) when present in open submitochondrial particles from bovine heart. The kinetic pattern follows a Ping Pong mechanism; contrary to the situation found with the isolated enzyme [Speck and Margoliash (1984) J. Biol. Chem. 259, 1064-1072, and confirmed in our laboratory], no substrate inhibition by oxidized cytochrome c was observed with the membrane-bound enzyme. Endogenous oxidized ubiquinone-10 is unable to exert product inhibition under the conditions employed. In the Ping Pong mechanism for this enzyme, the reaction scheme can be clearly divided into two parts, and the Kmin (keat/Km) value for one substrate is independent of the rate constant for the second substrate. Both ubiquinol-1 and ubiquinol-2 can be used as electron donors reacting with the enzyme from within the lipid bilayer [Fato, Castelluccio, Palmer and Lenaz (1988) Biochim. Biophys. Acta 932,[216][217][218][219][220][221][222]; the kmin values for ubiquinols, when calculated on the basis of their membranous concentrations, are significantly lower than the kmin for cytochrome c. The temperature-dependence of the kinetic parameters was investigated by titrating each of the substrates under quasi-saturating concentrations of the second substrate. Arrhenius plots of Vm.. extrapolated from both cytochrome c and ubiquinol titrations were linear, when care was taken to verify the quasi-saturating concentrations of the fixed co-substrate. The Arrhenius plots for the kmin values for both ubiquinol and cytochrome c were linear, but the activation energy was much higher for the former, particularly when calculated for ubiquinol dissolved in the lipid phase; the very low value of activation energy of the kmin for cytochrome c is strong support for diffusion control being present in the reaction of cytochrome c with the membranous enzyme. In contrast to the soluble enzyme, ubiquinone titrations of submitochondrial particles at low cytochrome c concentrations deviated from hyperbolic behaviour. Changing the medium viscosity with either poly(ethylene glycol) or sucrose had a strong effect on the cytochrome c kmin, whereas the change in the ubiquinol kmin was much smaller. From the viscosity studies the extent of diffusional control could be calculated, revealing that the reaction with cytochrome c was mostly diffusion-limited. The viscosity of the membrane was changed by incorporating cholesterol; no significant effect on the ubiquinol kmin ascribable to diffusion control could be recognized. The bulk of the studies reported here strongly suggest that ubiquinol-cytochrome c reductase is subject to diffusion control of the interaction of cytochrome c from the aqueous medium, but not of the interaction of the short-chain ubiquinols from the membrane interior. INTRODUCTIONSeveral enzy...

show abstract

Exclusion of poly(ethylene glycol) from liposome surfaces

Cited by 114 publications

References 25 publications

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Förster resonance energy transfer imaging

Steady-state kinetics of ubiquinol-cytochrome c reductase in bovine heart submitochondrial particles: diffusional effects

Contact Info

Product

Resources

About