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Interactions between Beta-2-Glycoprotein-1 and Phospholipid Bilayer-A Molecular Dynamic Study.

ABSTRACT: This study aims to investigate the interactions appearing when the beta-2-glycoprotein-1 binds to a lipid bilayer. The inter- and intra-molecular forces acting between the two macromolecular systems have been investigated using a molecular dynamics simulation method. The importance of water bridges has also been addressed. Additionally, the viscoelastic response of the bilayer has been studied. In detail, the (saturated-chain) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and (unsaturated-chain) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) bilayers have been chosen to test their behavior near the protein. Both of the lipids have a polar head but different chemical structures and are similar to the main phospholipids present in the synovial fluid. This study is meaningful for further explaining the worsening friction properties in articular cartilage, as the inactivation of phospholipid bilayers by beta-2-glycoprotein-1 is believed to be a cause of the destruction of cartilage in most rheumatic diseases and osteoarthritis. It was found that the protein binds stronger to the DPPC bilayer than to the POPE, but in both cases, it has the potential to change the local bilayer stability. Nevertheless, the binding forces are placed within a small area (only a few lipids contribute to the binding, creating many interactions). However, together, they are not stronger than the covalent bonds between C-O, thus, potentially, it is possible to push the lipids into the bilayer but detaching the lipids' heads from the tail is not possible. Additionally, the protein causes water displacement from the vicinity of the bilayer, and this may be a contributor to the instability of the bilayer (disrupting the water bridges needed for the stabilization of the bilayer, especially in the case of DPPC where the heads are not so well stabilized by H-bonds as they are in POPE). Moreover, it was found that the diffusivity of lipids in the DPPC bilayer bound to the protein is significantly different from the diffusivity of the ones which are not in contact with the protein. The POPE bilayer is stiffer due to intramolecular interactions, which are stronger than in the DPPC; thus, the viscous to elastic effects in the POPE case are more significant than in the case of the DPPC. It is, therefore, harder to destabilize the POPE bilayer than the DPPC one.

SUBMITTER: Kruszewska N

PROVIDER: S-EPMC7762114 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Interactions between Beta-2-Glycoprotein-1 and Phospholipid Bilayer-A Molecular Dynamic Study.

Kruszewska Natalia N Domino Krzysztof K Drelich Radosław R Urbaniak Wiesław W Petelska Aneta D AD

Membranes 20201205 12

This study aims to investigate the interactions appearing when the beta-2-glycoprotein-1 binds to a lipid bilayer. The inter- and intra-molecular forces acting between the two macromolecular systems have been investigated using a molecular dynamics simulation method. The importance of water bridges has also been addressed. Additionally, the viscoelastic response of the bilayer has been studied. In detail, the (saturated-chain) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and (unsaturated-c ...[more]

PMID: 33291449

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Project description:The study of Langmuir monolayers incorporating biomimetic and bioactive substances plays an important role today in assessing the properties and quality of the molecular films for potential biomedical applications. Here, miscibility of binary and ternary monolayers of phospholipid (dioleoyl phosphatidylcholine, DOPC), immunosuppressant (cyclosporine A, CsA), and antioxidant (lauryl gallate, LG) of varying molar fractions was analyzed by means of the Langmuir technique coupled with a surface potential (ΔV) module at the air-water interface. The surface pressure-area per molecule (π-A) isotherms provided information on the physical state of the films at a given surface pressure, the monolayer packing and ordering, and the type and strength of intermolecular interactions. Surface potential-area (ΔV-A) isotherms revealed the molecular orientation changes at the interface upon compression. In addition, the apparent dipole moment of the monolayer-forming molecules was determined from the surface potential isotherms. The obtained results indicated that the film compression provoked subsequent changes of CsA conformation and/or orientation, conferring better affinity for the hydrocarbon environment. The mutual interactions between the components were analyzed here in terms of the excess and total Gibbs energy of mixing, whose values depended on the stoichiometry of the mixed films. The strongest attraction, thus the highest thermodynamic stability, was found for a DOPC-CsA-LG mixture with a 1:1:2 molar ratio. Based on these results, a molecular model for the organization of the molecules within the Langmuir film was proposed. Through this model, we elucidated the significant role of LG in improving the miscibility of CsA in the model DOPC membrane and thus in increasing the stability of self-assembled monolayers by noncovalent interactions, such as H-bonds and Lifshitz-van der Waals forces. The above 1:1:2 combination of three components is revealed as the most promising film composition for the modification of implant device surfaces to improve their biocompatibility. Further insight into mechanisms concerning drug-membrane interactions at the molecular level is provided, which results in great importance for biocoating design and development as well as for drug release at target sites.

Dataset Information

Interactions between Beta-2-Glycoprotein-1 and Phospholipid Bilayer-A Molecular Dynamic Study.

Publications

Interactions between Beta-2-Glycoprotein-1 and Phospholipid Bilayer-A Molecular Dynamic Study.

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