Complex formation and other phase transformations mapped in saturated phosphatidylcholine/DSPE-PEG2000 monolayers

Lozano, Monica M.; Longo, Marjorie L.

doi:10.1039/b820070j

Cited by 55 publications

(118 citation statements)

References 30 publications

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“…28 The large size of polymeric domains suggests their potential to crowd membrane surfaces, producing steric pressure. Several studies have shown that membrane-conjugated polymers such as polyethylene glycol (PEG) chains can generate significant lateral steric pressure, sufficient to influence lipid phase behavior 29 and at very high densities, sufficient to induce formation of coexisting gel-gel phases owing to depletion attraction effects. 30–32 Additionally, simply attaching polymers to the membrane surface comes at an entropic cost 33 such that polymers prefer curved surfaces 34 and sterically repel other molecules including other PEG chains.…”

Section: Introductionmentioning

confidence: 99%

Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation

et al. 2016

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Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and polyethylene glycol (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogenous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of domain phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required to suppress phase separation decreases relative to longer polymers. Collectively, our results demonstrate that crowded, membrane-bound polymers are highly efficient suppressors of phase separation and suggest that the ability of lipid domains to resist steric pressure depends on both their lipid composition and the size and concentration of the membrane-bound polymers they incorporate.

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Section: Introductionmentioning

confidence: 99%

Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation

et al. 2016

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“…Indeed, a lipid monolayer can be subjected to more than double the surface pressure of a lipid bilayer (~30 mN/m), where these lipid-linked oligonucleotides are reported to insert essentially irreversibly 19. Lipid shelled microbubbles will shrink in size at a rate roughly inversely dependent upon the sum of the radius and the shell gas transfer resistance times water diffusivity until the monolayer surface pressure approaches ~72 mN/m, a pressure reachable by DSPC 29. This pressure corresponds to an interfacial tension of zero mN/m and zero Pa Laplace overpressure 23.…”

Section: Resultsmentioning

confidence: 99%

“…For comparison to the time scales used for incubation here, 20 minutes and 2 hours, an estimate of the ejection time for an average sized (4 µm radius) microbubble can be made based upon a recent theoretical analysis by Sakar et al33 where dissolution of similarly coated microbubbles in air-saturated media is modeled. We assume an average surface tension during dissolution of 36 mN/m and a decrease to one-fifth surface area (area change for a similar lipopolymer to reach a 5 mN/m ejection surface tension)29. Figure 8 of Sakar et al33 gives an average dissolution rate of approximately −2.5 µm/hr, and therefore a time of approximately 1 hour for the necessary decrease in area.…”

Section: Resultsmentioning

confidence: 99%

Vesicles Tethered to Microbubbles by Hybridized DNA Oligonucleotides: Flow Cytometry Analysis of This New Drug Delivery Vehicle Design

2010

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Hybridization of complementary lipid-linked DNA oligonucleotides was used to tether small unilamellar vesicles (SUVs) to the lipid monolayer shells of air-microbubbles, a new attachment design for a drug delivery vehicle to be used in tandem with ultrasound imaging. Flow cytometry was used and a novel analysis was developed, based upon light scattering and fluorescence intensity, to quantify the fraction of microbubbles of chosen size-ranges with oligonucleotide-tethered fluorescently labeled SUVs. Fluorescence microscopy was used to verify that our methodology results in successful high-density SUV tethering to a similar fraction of the microbubbles when compared to the flow cytometry statistics. The fraction of successful tetherings increased with the concentration of the complementary lipid-linked oligonucleotide as expected and decreased with the time that microbubbles were incubated with SUVs, which was not expected. Also unexpected, a large fraction of microbubbles had only background fluorescence levels while a much smaller fraction (at most one-eighth, for the shortest incubation and highest concentration of lipid-linked oligonucleotide) had oligonucleotide-tethered fluorescently labeled SUVs and, according to our fluorescence microscopy, that small fraction was densely covered with SUVs. Ejection of the lipidlinked oligonucleotide during high surface pressure compression of the monolayer shells of actively shrinking microbubbles subjected to the Laplace overpressure is speculated as a qualitatively explanation for the statistics.

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“…The use of chitosan is based on its potential to reduce lipid relaxation (e.g. lateral diffusion) (Baumgart & Offenhausser, 2003) and therefore, maintain a stiff structure that diminishes phospholipid instabilities, such as buckling and folding mechanisms over timer (Garg et al, 2013;Lozano & Longo, 2009). …”

Section: Introductionmentioning

confidence: 99%