02683nas a2200181   4500000000100000000000100001008004100002260001200043100001800055700002100073700002200094700002100116700001900137245010300156856004600259490001100305520218500316       2020                            d  c12/20201 aN. Kruszewska1 aKrzysztof Domino1 aRadosław Drelich1 aWieslaw Urbaniak1 aAneta Petelska00aInteractions between Beta-2-glycoprotein-1 and phospholipid bilayer  – a molecular dynamic study  uhttps://doi.org/10.3390/membranes101203960 v10(12)3 a<p>The study aims to investigate the interactions appearing when the Beta-2-glycoprotein-1 binds to a lipid bilayer. The inter- and intramolecular 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) DPPC and (unsaturated-chain) POPE bilayers have been chosen to test their behavior near the protein. Both of the lipids have a polar head, but of different chemical structure, and are similar to the main phospholipids present in the synovial fluid. This study is meaningful for further explanation of 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 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 few lipids contribute to the binding, creating many interactions) but they together are not stronger than the covalent bonds between C-O, thus potentially it is possible to pull the lipids from 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 instability of the bilayer (disrupting the water bridges needed for the stabilization of the bilayer). 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 ratio of the viscous to elastic effects in the case of the POPE is greater than in the case of the DPPC. It is therefore harder to destabilize the POPE bilayer than the DPPC one.</p>