Structural organization of sterol molecules in DPPC bilayers: a coarse-grained molecular dynamics investigation

Zhang, Yawen; Carter, James W.; Lervik, Anders; Brooks, Nicholas J.; Seddon, John M.; Bresme, Fernando

doi:10.1039/c5sm03051j

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…To quantify the intermolecular organisation of our systems we used both the radial distribution function 10 and Voronoi tessellation analysis. This Voronoi approach has been previously employed to identify 2D clusters 46 in lipid bilayers; here we use a 3D version of this method.…”

Section: Cluster Characterizationmentioning

confidence: 99%

Understanding the interactions between sebum triglycerides and water: a molecular dynamics simulation study

Tascini

Noro

Chen

et al. 2018

Phys. Chem. Chem. Phys.

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In recent years, sebum oil has been found to play a key role in the regulation of the hydration of the outermost layer of the skin, the stratum corneum. Understanding how a major component of the sebum oil, the triglyceride tri-cis-6-hexadecenoin (TG), interacts with water is an important step in gaining insight into the water regulation function of the sebum oil. Here we use molecular dynamics simulations to investigate the structural and interfacial properties of TG in bulk and at the air and water interface. Our model performs very well in reproducing experimental results, such as density, surface tensions and surface pressure area isotherms. We show that triglyceride molecules in the liquid phase assemble together, through the glycerol group, forming a single percolating network. TG-air interfaces orient the lipids with the interface enriched with the hydrophobic tails and the glycerol groups buried inside. When in contact with water, the TG molecules at the interface orient the glycerol group towards the water phase and adopt a characteristic trident conformation. Water is shown to penetrate the TG layer thanks to the interaction with the oxygen atoms of the TG molecules, which acts as a pathway for water diffusion. The activation energy for the passage of water is found to be ≈9.5kT at 310 K, showing that the layer is permeable to water diffusion.

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Section: Cluster Characterizationmentioning

confidence: 99%

Understanding the interactions between sebum triglycerides and water: a molecular dynamics simulation study

Tascini

Noro

Chen

et al. 2018

Phys. Chem. Chem. Phys.

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“…Previously, the MARTINI CG simulations showed that the sterol organization and sterol–lipid interactions are strongly influenced by the sterol size . In this work, we examined the influence of the molecular dipole moment on the lateral organization of CHOL and 6-KC in DMPC lipid bilayers.…”

Section: Resultsmentioning

confidence: 97%

“…Previously, the MARTINI CG simulations showed that the sterol organization and sterol−lipid interactions are strongly influenced by the sterol size. 35 In this work, we examined the influence of the molecular dipole moment on the lateral organization of CHOL and 6-KC in DMPC lipid bilayers. The sterol−sterol radial distribution functions (RDFs) were calculated for the head−head and tail−tail pairs at high sterol concentration (40 mol %), respectively, shown in Figure 10.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Recently, Seo and Shinoda employed the SPICA CG force field to model the domain formation induced by cholesterol, reporting an observation of phase separation in lipid bilayers fully consistent with experiment. Zhang et al investigated the structural organization of sterol molecules in dipalmitoylphosphatidylcholine bilayer membranes by employing the MARTINI force field, , showing the sensitivity of the lateral organization of sterol molecules to sterol size. Using the MARTINI model, Bennett et al calculated the free-energy barrier for the flip-flop motion of cholesterol (Δ G f ) in lipid bilayer membranes, showing that the CG results are comparable to that obtained from atomistic simulations.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Cholesterol and 6-Ketocholestanol on Membrane Dipole Potential and Sterol Flip-Flop Motion in Bilayer Membranes

Shen

Zhao

et al. 2019

Langmuir

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A variety of experimental and theoretical approaches have been employed to investigate the sterol flip-flop motion in lipid bilayer membranes. However, the sterol effect on the dipole potential of lipid bilayer membranes is less well studied and the influence of dipole potential on sterol flip-flop motion in lipid bilayer membranes is less well understood. In our previous works, we have demonstrated the performance of our coarse-grained (CG) model in the computation of the dipole potential. In this work, five 30 μs CG simulations of dimyristoylphosphatidylcholine (DMPC) bilayers were carried out at different sterol concentrations (in a range from 10 to 50% mole fraction). Then, a comparison was made between the effects of cholesterol (CHOL) and 6-ketocholestanol (6-KC) on the dipole potential of DMPC lipid bilayers as well as the sterol flip-flop motion. Our CG simulations show that the membrane dipole potential is impacted more significantly by 6-KC than by CHOL. This finding is consistent with recent experimental studies. Meanwhile, our work suggests that the sterol–sterol interactions (in particular, electrostatic interactions) should be critical to the formation of sterol–sterol clusters, which would hinder the sterol flip-flop motion inside the lipid bilayers. This is in support of the recent experimental study on the sterol transportation in lipid bilayer membranes.

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“…Specifically, membrane thickness, area per lipid, and average membrane area all decrease with increasing CHOL content (Table S6), in agreement with previously reported data. 98,99 Of note, replacement of 50 mol % DPPC with CHOL reduced area per lipid and membrane area by ∼33%. We did not observe the appearance of CHOL patches in our simulations, with CHOL being distributed uniformly throughout the bilayer, regardless of concentration (Figure 9).…”

Section: Physicochemical Characterization Of Bsa-coated Liposomes 331...mentioning

confidence: 99%

Impact of Lipid Composition on Vesicle Protein Adsorption: A BSA Case Study

Amărandi,

Neamṭu,

Ştiufiuc

et al. 2024

ACS Omega

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Investigating the interaction between liposomes and proteins is of paramount importance in the development of liposomal formulations with real potential for bench-to-bedside transfer. Upon entering the body, proteins are immediately adsorbed on the liposomal surface, changing the nanovehicles' biological identity, which has a significant impact on their biodistribution and pharmacokinetics and ultimately on their therapeutic effect. Albumin is the most abundant plasma protein and thus usually adsorbs immediately on the liposomal surface. We herein report a comprehensive investigation on the adsorption of model protein bovine serum albumin (BSA) onto liposomal vesicles containing the zwitterionic lipid 1,2-dipalmitoyl-sn-glycero-3phosphocholine (DPPC), in combination with either cholesterol (CHOL) or the cationic lipid 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP). While many studies regarding protein adsorption on the surface of liposomes with different compositions have been performed, to the best of our knowledge, the differential responses of CHOL and DOTAP upon albumin adsorption on vesicles have not yet been investigated. UV−vis spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a strong influence of the phospholipid membrane composition on protein adsorption. Hence, it was found that DOTAP-containing vesicles adsorb proteins more robustly but also aggregate in the presence of BSA, as confirmed by DLS and TEM. Separation of liposome−protein complexes from unadsorbed proteins performed by means of centrifugation and size exclusion chromatography (SEC) was also investigated. Our results show that neither method can be regarded as a golden experimental setup to study the protein corona of liposomes. Yet, SEC proved to be more successful in the separation of unbound proteins, although the amount of lipid loss upon liposome elution was higher than expected. In addition, coarse-grained molecular dynamics simulations were employed to ascertain key membrane parameters, such as the membrane thickness and area per lipid. Overall, this study highlights the importance of surface charge and membrane fluidity in influencing the extent of protein adsorption. We hope that our investigation will be a valuable contribution to better understanding protein−vesicle interactions for improved nanocarrier design.

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Structural organization of sterol molecules in DPPC bilayers: a coarse-grained molecular dynamics investigation

Cited by 9 publications

References 45 publications

Understanding the interactions between sebum triglycerides and water: a molecular dynamics simulation study

Understanding the interactions between sebum triglycerides and water: a molecular dynamics simulation study

Effect of Cholesterol and 6-Ketocholestanol on Membrane Dipole Potential and Sterol Flip-Flop Motion in Bilayer Membranes

Impact of Lipid Composition on Vesicle Protein Adsorption: A BSA Case Study

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