Domain Size Regulation in Phospholipid Model Membranes Using Oil Molecules and Hybrid Lipids

Scheidegger, Laura; Stricker, Laura; Beltramo, Peter J.; Vermant, Jan

doi:10.1021/acs.jpcb.2c02862

Cited by 7 publications

(9 citation statements)

References 108 publications

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“…These cases exhibited a gradual evolution in the contact angle, increasing far beyond typical measurements for membranes formed in hexadecane , and in some cases reaching as high as 80°. The behavior continued for as long as 2 h after formation and appears to occur at a similar time scale to the growth of lipid domains observed by Scheidegger . A sample video of this evolution with respect to time is provided in Video S1.…”

Section: Resultsmentioning

confidence: 99%

Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry

Segars,

Makhoul-Mansour,

Beyrouthy

et al. 2024

Langmuir

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Diverse collections of lipids self-assemble into domains within biological membranes, and these domains are typically organized in both the transverse and lateral directions of the membrane. The ability of the membrane to link these domains across the membrane's interior grants cells control over features on the external cellular surface. Numerous hypothesized factors drive the cross-membrane (or transverse) coupling of lipid domains. In this work we seek to isolate these transverse lipid−lipid influences in a simple model system using droplet interface bilayers (DIBs) to better understand the associated mechanics. DIBs enable symmetric and asymmetric combinations of domain-forming lipid mixtures within a model bilayer, and the evolving energetics of the membrane may be tracked using drop-shape analysis. We find that symmetric distributions of domain-forming lipids produce long-lasting, gradual shifts in the DIB membrane energetics that are not observed in asymmetric distributions of the lipids where the domain-forming lipids are only within one leaflet. The approach selected for this work provides experimental measurement of the mismatch penalty associated with antiregistered lipid domains as well as measurements of the influence of rafts on DIB behaviors with suggestions for their future use as a model platform.

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Section: Resultsmentioning

confidence: 99%

Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry

Segars,

Makhoul-Mansour,

Beyrouthy

et al. 2024

Langmuir

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“…It has been observed that bilayers formed from phospholipids dispersed in squalene exhibit very high specific capacitance values, indicative of a thin “solvent-free” bilayer. − That is because such a large hydrophobic molecule will experience a high entropic penalty in its interactions with lipid acyl chains and tend to be largely excluded from the bilayer. Any residual squalene in the bilayer would be most probably oriented parallel to the membrane plane (i.e., between its two leaflets), as seen by neutron diffraction measurements, and not situated at the water-lipid interface …”

Section: Resultsmentioning

confidence: 99%

“…Any residual squalene in the bilayer would be most probably oriented parallel to the membrane plane (i.e., between its two leaflets), as seen by neutron diffraction measurements, and not situated at the water-lipid interface. 74 Also shown in Table 2 are the interfacial parameters for cholesterol-enriched membranes (DOPC:chol at 1:1 mole ratio) in the presence of ASA, which can be compared to the analogous case of cholesterol-free DOPC. Similar effects are seen upon inclusion of ASA as with chol-free bilayers, but with a somewhat diminished intensity.…”

Section: ■ Introductionmentioning

confidence: 99%

Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner

Krmic,

Perez,

Scollan

et al. 2023

Langmuir

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Aspirin has been used for broad therapeutic treatment, including secondary prevention of cardiovascular disease associated with increased cholesterol levels. Aspirin and other nonsteroidal anti-inflammatory drugs have been shown to interact with lipid membranes and change their biophysical properties. In this study, mixed lipid model bilayers made from 1-palmitoyl-2oleoyl-sn-glycero-3-phosphatidylcholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) comprising varying concentrations of cholesterol (10:1, 4:1, and 1:1 mole ratio of lipid:chol), prepared by the droplet interface bilayer method, were used to examine the effects of aspirin at various pH on transbilayer water permeability. The presence of aspirin increases the water permeability of POPC bilayers in a concentration-dependent manner, with a greater magnitude of increase at pH 3 compared to pH 7. In the presence of cholesterol, aspirin is similarly shown to increase water permeability; however, the extent of the increase depends on both the concentration of cholesterol and the pH, with the least pronounced enhancement in water permeability at high cholesterol levels at pH 7. A fusion of data from differential scanning calorimetry, confocal Raman microspectrophotometry, and interfacial tensiometric measurements demonstrates that aspirin can promote significant thermal, structural, and interfacial property perturbations in the mixed-lipid POPC or DOPC membranes containing cholesterol, indicating a disordering effect on the lipid membranes. Our findings suggest that aspirin fluidizes phosphocholine membranes in both cholesterol-free and cholesterol-enriched states and that the overall effect is greater when aspirin is in a neutral state. These results confer a deeper comprehension of the divergent effects of aspirin on biological membranes having heterogeneous compositions, under varying physiological pH and different cholesterol compositions, with implications for a better understanding of the gastrointestinal toxicity induced by the long term use of this important nonsteroidal anti-inflammatory molecule.

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“…This approach to determining the modulus yields consistent values for DOPC (~10 5 Pa) [ 22 , 23 ] that are an order of magnitude lower than those reported in other systems [ 27 ] when hexadecane is used as the oil solvent. We suspect that this is partially due to the impact of residual oil molecules within the membrane, which causes the membrane thickness to swell [ 23 , 28 , 29 , 30 ], and also in part due to the membrane area (and therefore, volume) changing during compression. When squalene is used as the oil solvent, membrane thicknesses approach the solvent-free limit and measured Young’s moduli (~10 6 Pa) are on the same order of magnitude as solvent-free approaches; however, the moduli values are still on the lower edge of the range, indicating possible remaining contributions from the membrane area (volume) changes during compression.…”

Section: Resultsmentioning

confidence: 99%

Determining the Bending Rigidity of Free-Standing Planar Phospholipid Bilayers

Zabala-Ferrera¹,

Liu²,

Beltramo³

2023

Membranes

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We describe a method to determine membrane bending rigidity from capacitance measurements on large area, free-standing, planar, biomembranes. The bending rigidity of lipid membranes is an important biological mechanical property that is commonly optically measured in vesicles, but difficult to quantify in a planar, unsupported system. To accomplish this, we simultaneously image and apply an electric potential to free-standing, millimeter area, planar lipid bilayers composed of DOPC and DOPG phospholipids to measure the membrane Young’s (elasticity) modulus. The bilayer is then modeled as two adjacent thin elastic films to calculate bending rigidity from the electromechanical response of the membrane to the applied field. Using DOPC, we show that bending rigidities determined by this approach are in good agreement with the existing work using neutron spin echo on vesicles, atomic force spectroscopy on supported lipid bilayers, and micropipette aspiration of giant unilamellar vesicles. We study the effect of asymmetric calcium concentration on symmetric DOPC and DOPG membranes and quantify the resulting changes in bending rigidity. This platform offers the ability to create planar bilayers of controlled lipid composition and aqueous ionic environment, with the ability to asymmetrically alter both. We aim to leverage this high degree of compositional and environmental control, along with the capacity to measure physical properties, in the study of various biological processes in the future.

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Domain Size Regulation in Phospholipid Model Membranes Using Oil Molecules and Hybrid Lipids

Cited by 7 publications

References 108 publications

Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry

Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry

Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner

Determining the Bending Rigidity of Free-Standing Planar Phospholipid Bilayers

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