| Autor: |
Oliveira AA; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093-0340, USA.; Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, São Carlos 13560-970, Brazil., Róg T; Department of Physics, University of Helsinki, P.O. Box 64, FI-00014 Helsinki, Finland., da Silva ABF; Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, São Carlos 13560-970, Brazil., Amaro RE; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093-0340, USA., Johnson MS; Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, Åbo Akademi University, 20520 Turku, Finland., Postila PA; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093-0340, USA.; Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, Åbo Akademi University, 20520 Turku, Finland.; Institute of Biomedicine, Kiinamyllynkatu 10, Integrative Physiology and Pharmacy, University of Turku, FI-20520 Turku, Finland.; Aurlide Ltd., FI-21420 Lieto, Finland.; InFLAMES Research Flagship Center, University of Turku, FI-20520 Turku, Finland. |
| Abstrakt: |
The outer mitochondrial membrane (OMM) is involved in multiple cellular functions such as apoptosis, inflammation and signaling via its membrane-associated and -embedded proteins. Despite the central role of the OMM in these vital phenomena, the structure and dynamics of the membrane have regularly been investigated in silico using simple two-component models. Accordingly, the aim was to generate the realistic multi-component model of the OMM and inspect its properties using atomistic molecular dynamics (MD) simulations. All major lipid components, phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), were included in the probed OMM models. Because increased levels of anionic PS lipids have potential effects on schizophrenia and, more specifically, on monoamine oxidase B enzyme activity, the effect of varying the PS concentration was explored. The MD simulations indicate that the complex membrane lipid composition (MLC) behavior is notably different from the two-component PC-PE model. The MLC changes caused relatively minor effects on the membrane structural properties such as membrane thickness or area per lipid; however, notable effects could be seen with the dynamical parameters at the water-membrane interface. Increase of PS levels appears to slow down lateral diffusion of all lipids and, in general, the presence of anionic lipids reduced hydration and slowed down the PE headgroup rotation. In addition, sodium ions could neutralize the membrane surface, when PI was the main anionic component; however, a similar effect was not seen for high PS levels. Based on these results, it is advisable for future studies on the OMM and its protein or ligand partners, especially when wanting to replicate the correct properties on the water-membrane interface, to use models that are sufficiently complex, containing anionic lipid types, PI in particular. |
