Effect of acetone accumulation on structure and dynamics of lipid membranes studied by molecular dynamics simulations |
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| Institution: | 1. Institute of Chemistry, V.N. Karazin Kharkiv National University, 4 Svobody Square, Kharkiv 61022, Ukraine;2. School of Chemistry, V.N. Karazin Kharkiv National University, 4 Svobody Square, Kharkiv 61022, Ukraine;1. Department of Physics, Alzahra University, Tehran 1993893973, Iran;2. Department of Physics, Sharif University of Technology, Tehran 1458889694, Iran;3. Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran 1458889694, Iran;1. School of Chemical Engineering and Pharmaceutics, Henan University of Science & Technology, Luoyang 471023, China;2. Department of Chemistry, Tsinghua University, Beijing 100084, China;1. Institute of High-Temperature Electrochemistry, Russian Academy of Sciences, Ural Division, Yekaterinburg 620990, Russia;2. Department of Chemistry, Ural Federal University, Yekaterinburg 620002, Russia;1. School of Sciences, Changchun University, Changchun 130022, China;2. State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012, China;1. Siberian Federal University, Svobodni av., 79, 660041 Krasnoyarsk, Russia;2. Siberian State Technological University, Mira av., 82, 660049 Krasnoyarsk, Russia |
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| Abstract: | The modulation of the properties and function of cell membranes by small volatile substances is important for many biomedical applications. Despite available experimental results, molecular mechanisms of action of inhalants and organic solvents, such as acetone, on lipid membranes remain not well understood. To gain a better understanding of how acetone interacts with membranes, we have performed a series of molecular dynamics (MD) simulations of a POPC bilayer in aqueous solution in the presence of acetone, whose concentration was varied from 2.8 to 11.2 mol%. The MD simulations of passive distribution of acetone between a bulk water phase and a lipid bilayer show that acetone favors partitioning into the water-free region of the bilayer, located near the carbonyl groups of the phospholipids and at the beginning of the hydrocarbon core of the lipid membrane. Using MD umbrella sampling, we found that the permeability barrier of ～0.5 kcal/mol exists for acetone partitioning into the membrane. In addition, a Gibbs free energy profile of the acetone penetration across a bilayer demonstrates a favorable potential energy well of ?3.6 kcal/mol, located at 15–16 Å from the bilayer center. The analysis of the structural and dynamics properties of the model membrane revealed that the POPC bilayer can tolerate the presence of acetone in the concentration range of 2.8–5.6 mol%. The accumulation of the higher acetone concentration of 11.2 mol% results, however, in drastic disordering of phospholipid packing and the increase in the membrane fluidity. The acetone molecules push the lipid heads apart and, hence, act as spacers in the headgroup region. This effect leads to the increase in the average headgroup area per molecule. In addition, the acyl tail region of the membrane also becomes less dense. We suggest, therefore, that the molecular mechanism of acetone action on the phospholipid bilayer has many common features with the effects of short chain alcohols, DMSO, and chloroform. |
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| Keywords: | Lipid bilayer Molecular dynamics simulations Acetone Toxicomania Inhalant |
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