title: Insertion of Neurotransmitters into a Lipid Bilayer Membrane and Its Implication on Membrane Stability: A Molecular Dynamics Study.
abstract: The signaling molecules in neurons, called neurotransmitters, play an essential role in the transportation of neural signals, during which the neurotransmitters interact with not only specific receptors, but also cytomembranes, such as synaptic vesicle membranes and postsynaptic membranes. Through extensive molecular dynamics simulations, the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh), and aspartic acid (ASP), into lipid bilayers is investigated. The results show that the first three neurotransmitters (ME, LE, and DA) are able to diffuse freely into both 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membranes, and are guided by the aromatic residues Tyr and Phe. Only a limited number of these neurotransmitters are allowed to penetrate into the membrane, which suggests an intrinsic mechanism by which the membrane is protected from being destroyed by excessive inserted neurotransmitters. After spontaneous insertion, the neurotransmitters disturb the surrounding phospholipids in the membrane, as indicated by the altered distribution of components in lipid leaflets and the disordered lipid tails. In contrast, the last two neurotransmitters (ACh and ASP) cannot enter the membrane, but instead always diffuse freely in solution. These findings provide an understanding at the atomic level of how neurotransmitters interact with the surrounding cytomembrane, as well as their impact on membrane behavior.
authors.affiliation: State Key Laboratory of Mechanics and Control of Mechanical Structure and Key Laboratory for Intelligent Nano Materials and Devices of the, Ministry of Education, and Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, 29 Yudao Street, Nanjing, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Mechanics and Control of Mechanical Structure and Key Laboratory for Intelligent Nano Materials and Devices of the, Ministry of Education, and Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, 29 Yudao Street, Nanjing, P.R. China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Mechanics and Control of Mechanical Structure and Key Laboratory for Intelligent Nano Materials and Devices of the, Ministry of Education, and Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, 29 Yudao Street, Nanjing, P.R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Mechanics and Control of Mechanical Structure and Key Laboratory for Intelligent Nano Materials and Devices of the, Ministry of Education, and Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, 29 Yudao Street, Nanjing, P.R. China.
authors.forename: Wanlin
authors.initials: W
authors.lastname: Guo
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D018377:Neurotransmitter Agents / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D018377:Neurotransmitter Agents; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C000608529:1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
keywords: biophysics; lipids; membranes; molecular dynamics; neurotransmitters