Molecular interactions of phospholipid monolayers with a model phospholipase

Zhang, Pin; Villanueva, Veronica; Kalkowski, Joseph; Liu, Chang; Donovan, Alexander J.; Bu, Wei; Schlossman, Mark L.; Lin, Binhua; Liu, Ying

doi:10.1039/c8sm01154k

Cited by 9 publications

(13 citation statements)

References 54 publications

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“…Even though the data discussed above have indicated the GO flakes to lay horizontal below the positively charged lipid layer, they may also insert into the layer. The insertion of any molecules into the lipid layer highly depends on its surface pressure. − Therefore, the interaction of GO flakes with the DSEPC lipid layer has been investigated as a function of surface pressure to confirm the organization of the flakes in and around the layer. The XRR profiles along with corresponding EDPs of DSEPC lipid layer on the GO-dissolved water surface (0.08 mg/mL) are shown in Figure a,b.…”

Section: Resultsmentioning

confidence: 99%

Self-Assembly of Graphene Oxide Nanoflakes in a Lipid Monolayer at the Air–Water Interface

Mandal

Giri

Murphy

et al. 2021

ACS Appl. Mater. Interfaces

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The graphene family, especially graphene oxide (GO), has captured increasing prospects in the biomedical field due to its excellent physicochemical properties. Understanding the health and environmental impact of GO is of great importance for guiding future applications. Although their interactions with living organisms are omnipresent, the exact molecular mechanism is yet to be established. The cellular membrane is the first barrier for a foreign molecule to interact before entering into the cell. In the present study, a model system consisting of a lipid monolayer at the air–water interface represents one of the leaflets of this membrane. Surface pressure–area isotherms and advanced synchrotron X-ray scattering techniques have been employed to comprehend the interaction by varying the electrostatics of the membrane. The results depict a strong GO interaction with positively charged phospholipids, weak interaction with zwitterionic lipids, and interestingly negligible interaction with negatively charged lipids. GO flakes induce significant changes in the out-of-plane organization of a positively charged lipid monolayer with a minor influence on in-plane assembly of lipid chains. This interaction is packing-specific, and the influence of GO is much stronger at lower surface pressure. Even though for zwitterionic phospholipids, the GO flakes may partly insert into the lipid chains, the X-ray scattering results indicate that the flakes preferentially lie horizontally underneath the positively charged lipid monolayer. This in-depth structural description may pave new perspectives for the scientific community for the development of GO-based biosensors and biomedical materials.

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Section: Resultsmentioning

confidence: 99%

Self-Assembly of Graphene Oxide Nanoflakes in a Lipid Monolayer at the Air–Water Interface

Mandal

Giri

Murphy

et al. 2021

ACS Appl. Mater. Interfaces

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“…The X-ray wavelength was 1.24 Å. Details of the experimental setup were described in our previous publications. − Briefly, a custom-made Langmuir trough (78 mm × 177.6 mm) with a single barrier was filled with 60 mL of PBS buffer. The trough is placed inside a gastight box.…”

Section: Methodsmentioning

confidence: 99%

Knowledge-Based Design of 5-Fluororacil Prodrug Liposomal Formulation: Molecular Packing and Interaction Revealed by Interfacial Isotherms and X-ray Scattering Techniques

et al. 2021

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Prodrugs and nanoformulations are two effective strategies for sustained drug release and targeting drug delivery. In this study, we combined the two strategies to judiciously design the liposome formulation incorporating an amphiphilic prodrug of 5fouroracil (5-FU), named 5-FCPal, for sustained drug release and enhanced bioavailability. 5-FCPal is an analogue of capecitabine (N 4 -pentyloxycarbonyl-5′-deoxy-5-fluorocytidine, Xeloda) by substituting the pentyl group at the N 4 position with the palmityl. The amphiphilic molecule of 5-FCPal can self-assemble with the phospholipids to form stable vesicle structures with high drug loading. Although lipid vesicles have been widely studied and commercially used for clinical applications, because of the enormous options of the lipids and the equitable balance of hydrophobicity and bioavailability, it is essential to fundamentally understand the molecular interactions when designing and optimizing the liposomal prodrug formulations. We report the study of using X-ray liquid surface scattering techniques integrated with a Langmuir trough to explicitly reveal the interfacial behavior of the monolayer membrane of 5-FCPal with various saturated and unsaturated lipids with positively charged, neutral, and negatively charged head groups. More specifically, interfacial packing of the molecules was quantified using interfacial isotherms, X-ray reflectivity (XR), and grazingincidence diffraction (GIXD). The results indicate that the interactions between the prodrug and the cationic lipids are most favorable. The highest drug loading is quantified by increasing the molar ratio of the prodrug until stable monolayer structures were disrupted by the multiple-layer domain of prodrug aggregates. Stable liposomes of 100 nm with 50% drug loading of 5-FCPal were generated based on the findings from the X-ray studies.

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“…After lipid film degradation catalyzed by sPLA 2 , domains of degraded products emerged. 32 Thus, a multiphase box model with incoherent addition of reflectivity from different domains was used to fit the reflectivity data, 37…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The positions and intensity ratios of the five Bragg peaks obtained from the degraded DPPC film were similar to those of peaks obtained from a PA film on the same Ca buffer. 32,33 When including 5% or 10% DPPE-PEG5k in the films, an additional in-plane peak emerged at 1.5 Å −1 (Figure 4B and C). Further increasing the molar fraction of DPPE-PEG5k to 15% resulted in more pronounced intensity of this single in-plane peak (Figure 4B and C).…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…XR and GIXD experiments were conducted using a Langmuir trough integrated with the synchrotron X-ray beamline at the National Science Foundation’s (NSF’s) ChemMatCARS (sector 15C of Advanced Photon Sources) at Argonne National Laboratory. Details of the experimental setup were described in our previous studies. − The X-ray wavelength was 1.24 Å, and all experiments were conducted at about 22.7 °C.…”

Section: Materials and Methodsmentioning

confidence: 99%

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Impeded Molecular Reorganization by Polyethylene Glycol Conjugation Revealed by X-ray Reflectivity and Diffraction Measurements

et al. 2020

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Polyethylene glycol (PEG) coatings have been widely applied in pharmaceutical and biomedical systems to prevent nonspecific protein absorption, increase vesicle blood circulation time, and sustain drug release. This study systematically investigated the planar interfacial organization of phospholipid monolayers containing various amounts of PEG conjugations before and after enzyme-catalyzed degradation of the lipids using X-ray reflectivity and grazing incidence X-ray diffraction techniques. Results showed that attaching PEG to the headgroup of the lipids up to 15 mol % had limited effects on molecular packing of the lipid monolayers in the condensed phase at the gas−liquid interface and negligible effects on the enzyme adsorption to the interface. After enzyme-catalyzed degradation, equimolar fatty acids and lyso PC were generated. The fatty acids together with the subphase Ca 2+ self-assembled into highly organized multilayer domains at the interface. The X-ray measurements unambiguously revealed that the densely packed PEG markedly hindered microphase separation and formation of the palmitic acid−Ca 2+ complexes.

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Molecular interactions of phospholipid monolayers with a model phospholipase

Abstract: Degradation of DPPC catalyzed by sPLA2 resulted in a mixture of highly-ordered multilayer domains and a loosely packed monolayer phase.

Cited by 9 publications

References 54 publications

Self-Assembly of Graphene Oxide Nanoflakes in a Lipid Monolayer at the Air–Water Interface

Self-Assembly of Graphene Oxide Nanoflakes in a Lipid Monolayer at the Air–Water Interface

Knowledge-Based Design of 5-Fluororacil Prodrug Liposomal Formulation: Molecular Packing and Interaction Revealed by Interfacial Isotherms and X-ray Scattering Techniques

Impeded Molecular Reorganization by Polyethylene Glycol Conjugation Revealed by X-ray Reflectivity and Diffraction Measurements

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