Effect of Ions on a Dipalmitoyl Phosphatidylcholine Bilayer. A Molecular Dynamics Simulation Study

Abstract

The effect of physiological concentrations of different chlorides on the structure of a dipalmitoyl phosphatidylcholine (DPPC) bilayer has been investigated through atomistic molecular dynamics simulations. These calculations provide support to the concept that Li+, Na+, Ca2+, Mg2+, Sr2+, Ba2+, and Ac3+, but not K+, bind to the lipid-head oxygens. Ion binding exhibits an influence on lipid order, area per lipid, orientation of the lipid head dipole, the charge distribution in the system, and therefore the electrostatic potential across the head-group region of the bilayer. These structural effects are sensitive to the specific characteristics of each cation, i.e., radius, charge, and coordination properties. These results provide evidence aimed at shedding some light into the apparent contradictions among different studies reported recently regarding the ordering effect of ions on zwitterionic phosphatidylcholine lipid bilayers.

Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

“…In particular, it has been demonstrated that cations (e.g., Na + ions) are able to penetrate rather deep in the lipid headgroup region. This effect has been observed in zwitterionic, 33,42,46,[50][51][52][53] anionic, 55,56,58 and slightly cationic 61 lipid bilayers. The findings agree with experimental data.…”

“…43,45,57 In contrast, using the "Berger lipids", i.e., variants of united-atom force-fields based on refs 70, 96, and 97, tight binding of Na + ions to the lipid carbonyl oxygens is found. 33,42,46,[50][51][52][53]55,56,58,61 Due to the different nature of these two force-fields, simulations using CHARMM27 lipids need to be performed with the area of the bilayer fixed, whereas Berger lipids allow simulations in the NpT ensemble, such that the bilayer can adjust its area to agree with the thermodynamic parameters. Furthermore, the carbonyl region of lipid molecules is more polar in the case of the Berger force-field, so that it attracts cations considerably stronger compared to its CHARMM counterpart.…”

“…[28][29][30][31][32][33][34][35][36][37][38][39][40][41] As for molecular-level computational studies, the increase in computing power in the past few years has made it possible to extend computer simulations beyond the relatively long relaxation times of tens to hundreds of nanoseconds required for equilibration of ions in lipid/water systems. Although most computational studies by far have focused on the effects of salt ions on zwitterionic (neutral) lipid bilayers, 33,[42][43][44][45][46][47][48][49][50][51][52][53] there is also an increasing number of studies on anionic [54][55][56][57][58][59] and cationic 60,61 lipid bilayers. Most simulations have addressed the effect of ions on the structural and electrostatic properties of lipid membranes.…”

Molecular electrometer and binding of cations to phospholipid bilayers

“…At sub-molar NaCl concentrations, the rotational and translational dynamics of membraneembedded fluorescent probes decreased 7,9,12 , and atomic force microscopy (AFM) experiments showed changes in bilayer hard-ness [14][15][16][17][18] ; in atomistic molecular dynamics (MD) simulations, phospholipid bilayers consistently bound Na + , although the binding strength depended on the model used 12,13,[21][22][23][24][25][26] .…”

“…Similarly, the lack of significant positive electrophoretic mobility of phosphatidylcholine (PC) vesicles in the presence of NaCl (again in contrast to multivalent ions and Li + ) suggested weak binding of Na + 1,8,14,15,27 ; however, these data were also explained by a countering effect of the Cl − ions 22,28 . Furthermore, to reduce the area per lipid in scattering experiments, molar concentrations of NaCl were required 10 , indicating weak ion-lipid interaction; in MD simulations, however, already orders of magnitude lower concentrations resulted in Na + binding and a clear reduction of area per lipid 12,23 . Finally, lipid lateral diffusion was unaltered by NaCl in noninvasive NMR experiments 11 ; however, as it was reduced upon Na + binding in simulations, the reduced lateral diffusion of fluorescent probes 7,9,12 has been interpreted to support the post-2000 'strong binding' view.…”