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.

Keywords: POPC bilayer; ion force field; lipid force field; molecular dynamics; salt effects; sodium chloride.

Figure 1

Profiles of water (${\rho }_{\mathrm{OW}}(z)$) and ion (${\rho }_I(z)$; $I=$ Na${}^{+}$ or Cl${}^{-}$) number densities normal to the membrane, along with integrated ion density profiles giving the cumulative number of ions ($N_I(z)$; $I=$ Na${}^{+}$ or Cl${}^{-}$), for simulation S${}_{\mathrm{NaCl}}$(o,wc), i.e., a simulation based on the unmodified force field (Table 7). The dashed vertical lines indicate z-values where the water oxygen number density evaluates to half of its bulk value, i.e., the location of the shear plane $z_{\mathrm{s}}$ (Section 4.3.2). The corresponding apparent binding constants are reported in Table 2. Note that in this illustration, the lipid bilayer is centered.

Figure 2

As Figure 1, but for simulation S${}_{\mathrm{NaCl}}$(m1,wc), i.e., a simulation based on a modified force field (Table 7). The corresponding apparent binding constants are reported in Table 2.

Figure 3

As Figure 1, but for simulation S${}_{\mathrm{NaCl}}$(m2,wc), i.e., a simulation based on a modified force field (Table 7). The corresponding apparent binding constants are reported in Table 2.

Figure 4

Symmetrized electrostatic potential $\varphi (z)$ along the bilayer normal (Equation (16)), for simulations S${}_{\mathrm{wat}}$(wc), S${}_{\mathrm{NaCl}}$(o,wc), S${}_{\mathrm{NaCl}}$(m1,wc) and S${}_{\mathrm{NaCl}}$(m2,wc), shown as black, red, green and blue curves, respectively. The underlying atom-based charge density ${\rho }_{\mathrm{a}}(z)$ involves (a) all atoms, (b) ions or (c) only lipid (dashed lines; labeled “POPC”) or water (solid lines; labeled “water”) atoms. The anchoring of the curves was done as described in Section 4.3.1. The simulation acronyms are explained in Table 7. Note that in this illustration, the lipid bilayer is centered.

Figure 5

Spectral intensity of membrane undulations $\langle u^2(q)\rangle$ as a function of the wavenumber q for simulations L${}_{\mathrm{wat}}$(wc), L${}_{\mathrm{NaCl}}$(o,wc), L${}_{\mathrm{NaCl}}$(m1,wc) and L${}_{\mathrm{NaCl}}$(m2,wc), shown as black, red, green and blue circles, respectively. $\langle u^2(q)\rangle$ was obtained from a Fourier transform of the discretized undulation $\overline{\tilde{z}}(x_i,y_j)$ (Section 4.3.1). The data refer to the results from the analysis employing twelve grid cells per dimension. Solid lines indicate a fit according to Equation (18), carried out in the low-wavenumber regime. The simulation acronyms are explained in Table 7.

Figure 6

Deuterium order parameter $-S_i$ (Equation (11)) of the CH${}_n$ groups i of the oleoyl (a) and palmitoyl (b) chains for simulations S${}_{\mathrm{wat}}$(wc), S${}_{\mathrm{NaCl}}$(o,wc), S${}_{\mathrm{NaCl}}$(m1,wc) and S${}_{\mathrm{NaCl}}$(m2,wc), shown as black, red, green and blue circles, respectively. The first (carboxylate) and last CH${}_n$ groups are omitted from the analysis. The simulation acronyms are explained in Table 7.