Effect of Sodium and Chloride Binding on a Lecithin Bilayer. A Molecular Dynamics Study

Abstract

The effect of ion binding on the structural, mechanical, dynamic and electrostatic properties of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer in a 0.5 M aqueous NaCl solution is investigated using classical atomistic molecular dynamics simulation with different force-field descriptions for ion-ion and ion-lipid interactions. Most importantly, the repulsive Lennard–Jones parameters for the latter were modified, such that approximately similar binding of cations and anions to the lipid membrane is achieved. This was done to qualitatively improve the apparent ion-lipid binding constants obtained from simulations with the original force field (Berger lipids and GROMOS87 ions in combination with the SPC water model) in comparison to experimental data. Furthermore, various parameters characterizing membrane structure, elasticity, order and dynamics are analyzed. It is found that ion binding as observed in simulations involving the modified in comparison to the original force-field description leads to: (i) a smaller salt-induced change in the area per lipid, which is in closer agreement with the experiment; (ii) a decrease in the area compressibility and bilayer thickness to values comparable to a bilayer in pure water; (iii) lipid deuterium order parameters and lipid diffusion coefficients on nanosecond timescales that are very similar to the values for a membrane in pure water. In general, salt effects on the structural properties of a POPC bilayer in an aqueous sodium-chloride solution appear to be reproduced reasonably well by the new force-field description. An analysis of membrane-membrane disjoining pressure suggests that the smaller salt-induced change in area per lipid induced by the new force-field description is not due to the alteration of membrane-associated net charge, but must rather be understood as a consequence of ion-specific effects on the arrangement of lipid molecules.

Competing for the same space: protons and alkali ions at the interface of phospholipid bilayers

“…(B) Typical structure of a Na + ion coordinated by the carbonyl oxygen of two lipids and water molecules. Reprinted from Böckmann et al (2003) with permission from Elsevier elasticity (Reif et al 2017). Much like the reported difference in binding affinities for Na + and K + to the lipid interface, relative to Na + , K + induces a weaker effect on membrane structure (Petrache et al 2006).…”

“…Reprinted from Wolf et al (2014) with permission from Elsevier monovalent ions (Garcia-Manyes et al 2005;Garcia-Manyes et al 2006;Garcia et al 2019;Piantanida et al 2017). In addition, simulations have demonstrated changes to the area per lipid, order parameters, diffusion coefficients and orientations of the headgroup dipole (Böckmann et al 2003;Cordomí et al 2008;Gurtovenko and Vattulainen 2008;Reif et al 2017;Vácha et al 2009).…”

“…Similar to the study of proton-membrane interactions, molecular details on where and how alkali ions bind to phospholipids have predominantly been obtained from MD simulations. A large number of studies demonstrated the binding of Na + and/ or K + ions to the water-lipid interface of zwitterionic and anionic phospholipid bilayers at physiologically relevant salt concentrations (Böckmann et al 2003;Cordomí et al 2008Cordomí et al , 2009Gambu and Roux 1997;Gurtovenko and Vattulainen 2008;Javanainen et al 2017;Jurkiewicz et al 2012;Klasczyk and Knecht 2011;Lee et al 2008;Mao et al 2013;Mukhopadhyay et al 2004;Pabst et al 2007;Pandit et al 2003;Reif et al 2017;Vácha et al 2010Vácha et al , 2009Vorobyov et al 2014). Combined results from these studies suggest that alkali ions form stable interactions with the phosphate and carbonyl groups in the phospholipid headgroups (Böckmann et al 2003;Cordomí et al 2008Cordomí et al , 2009Gambu and Roux 1997;Javanainen et al 2017;Jurkiewicz et al 2012;Lee et al 2008;Mukhopadhyay et al 2004;Pandit et al 2003;Vácha et al 2010).…”

“…Both protons and alkali ions are small cations that have been shown to bind to the water-lipid interface of phospholipid membranes and, through these water-ion-lipid interactions, have the capacity to change the structure and physicochemical properties of membranes (Böckmann et al 2003;Cordomí et al 2009;Cranfield et al 2016;Deplazes et al 2017;Garcia-Manyes et al 2005;Garcia-Manyes et al 2006;Garcia et al 2019;Koynova and Caffrey 1998;Petelska and Figaszewski 2002;Piantanida et al 2017;Reif et al 2017;Vácha et al 2009). As we will outline in this review, in many cases, the reported findings on how protons and alkali ions interact with phospholipid membranes This article is part of a Special Issue dedicated to the '2018 Joint Conference of the Asian Biophysics Association and Australian Society for Biophysics' edited by Kuniaki Nagayama, Raymond Norton, Kyeong Kyu Kim, Hiroyuki Noji, Till Böcking, and Andrew Battle.…”

The N-Terminal Segment of the Voltage-Dependent Anion Channel: A Possible Membrane-Bound Intermediate in Pore Unbinding

“…A lattice-sum electrostatics scheme was refrained from to minimize periodicity artifacts. Counterions were not included in simulations to avoid spurious ion-membrane interactions due to possibly inappropriate forcefield parameters [39]. An overview of the performed simulations is provided in Table 1.…”