title: Effect of NaCl and KCl on phosphatidylcholine and phosphatidylethanolamine lipid membranes: insight from atomic-scale simulations for understanding salt-induced effects in the plasma membrane.
abstract: To gain a better understanding of how monovalent salt under physiological conditions affects plasma membranes, we have performed 200 ns atomic-scale molecular dynamics simulations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipid bilayers. These two systems provide representative models for the outer and inner leaflets of the plasma membrane, respectively. The implications of cation-lipid interactions in these lipid systems have been considered in two different aqueous salt solutions, namely NaCl and KCl, and the sensitivity of the results on the details of interactions used for ions is determined by repeating the simulations with two distinctly different force fields. We demonstrate that the main effect of monovalent salt on a phospholipid membrane is determined by cations binding to the carbonyl region of a membrane, while chloride anions mostly stay in the water phase. It turns out that the strength and character of the cation-lipid interactions are quite different for different types of lipids and cations. PC membranes and Na+ ions demonstrate strongest interactions, leading to notable membrane compression. This finding was confirmed by both force fields (Gromacs and Charmm) employed for the ions. The binding of potassium ions to PC membranes (and the overall effect of KCl), in turn, was found to be much weaker mainly due to the larger size of a K+ ion compared to Na+. Furthermore, the effect of KCl on PC membranes was found to be force-field sensitive: The binding of a potassium ion was not observed at all in simulations performed with the Gromacs force-field, which seems to exaggerate the size of a K+ ion. As far as PE lipid bilayers are concerned, they are found to be influenced by monovalent salt to a significantly lesser extent compared to PC bilayers, which is a direct consequence of the ability of PE lipids to form both intra- and intermolecular hydrogen bonds and hence to adopt a more densely packed bilayer structure. Whereas for NaCl we observed weak binding of Na+ cations to the PE lipid-water interface, in the case of KCl we witnessed almost complete lack of cation binding. Overall, our findings indicate that monovalent salt ions affect lipids in the inner and outer leaflets of plasma cell membranes in substantially different ways.
authors.affiliation: Computational Biophysics Laboratory, Institute of Pharmaceutical Innovation, University of Bradford, West Yorkshire BD7 1DP, UK. A.Gurtovenko@bradford.ac.uk
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Gurtovenko
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011189:Potassium Chloride / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D012965:Sodium Chloride; D011189:Potassium Chloride