Specific Ion Effects in Cholesterol Monolayers

Abstract

The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl₂ and MgCl₂) on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance) and theoretically (molecular dynamics (MD) all-atomic simulations). We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

Keywords: Langmuir monolayers; cholesterol; ionic specificity; molecular dynamics simulations; surface forces.

Figure 1

Surface pressure (π) vs. area per molecule (MMA) isotherm of cholesterol (CHOL) monolayers in a 15 mM NaCl subphase. The arrows indicate the particular cases analyzed by molecular dynamics (MD) simulations: 33.1 Ų/molecule; 35.3 Ų/molecule and; 40 Ų/molecule (standard deviation <2%).

Figure 2

Snapshots from MD simulations (T = 298 K) corresponding to different area per molecule: (a) 40 Ų/molecule; (b) 35.3 Ų/molecule and; (c) 33.1 Ų/molecule. CHOL molecules are shown in bond representation; water is shown as lines and ions as spheres with Van der waals radii (yellow spheres: Na⁺; blue spheres: Cl⁻). The shaded region indicates the employed periodic boundary conditions. This figure was made with VMD software [29].

Figure 3

Radial distribution functions g(r) between NaCl electrolyte and CHOL headgroup obtained in three different MD simulations with different surface areas of CHOL monolayers: 33.1 Ų/molecule (red open circles); 35.3 Ų/molecule (black open circles) and; 40 Ų/molecule (blue crosses) (T = 298 K). (a) g(r) between Na⁺ of NaCl and oxygen atom in –OH headgroup of CHOL; (b) g(r) between Cl⁻ of NaCl and H atom in –OH headgroup of CHOL. The insets shows the molecular structure of CHOL as a reference. The relevant atom of the headgroup (H or O) is indicated with an arrow.

Figure 4

Snapshots from MD simulations (T = 298 K) corresponding to simulations at a fixed area per molecule (40 Ų/molecule) but different electrolyte. CHOL molecules are shown in bond representation; water is shown as lines and ions as spheres with Van der Waals radii. (a) NaCl (yellow spheres: Na⁺; blue spheres: Cl⁻); (b) NaI (yellow spheres: Na⁺; orange spheres: I⁻); (c) CaCl₂ (green spheres: Ca²⁺; blue spheres Cl⁻) and; (d) MgCl₂ (orange spheres: Mg²⁺; blue spheres: Cl⁻). The shaded region indicates periodic boundary conditions. This figure was made with VMD software [29].

Figure 5

Radial distribution functions g(r) between NaCl or NaI ions and CHOL headgroup obtained in MD simulations (T = 298 K) (a) g(r) between Cl⁻ from NaCl (black open circles) or I⁻ from NaI (green open circles) and H atom in –OH headgroup of CHOL; (b) g(r) between Na⁺ from NaCl (black open circles) or NaI (green open circles), and oxygen atom in –OH headgroup of CHOL.

Figure 6

Radial distribution functions g(r) between ions from NaCl, CaCl₂ or MgCl₂ and CHOL headgroup obtained in three different MD simulations (T = 298 K). In the presence of NaCl (black open circles), CaCl₂ (red open circles) or MgCl₂ (blue crosses). (a) g(r) between different cations and oxygen atom in –OH headgroup of CHOL: Na⁺ from NaCl (black open circles), Ca²⁺ from CaCl₂ (red open circles) or Mg²⁺ from MgCl₂ (blue crosses); (b) g(r) between Cl⁻ from different electrolyte (NaCl, black open circles, CaCl₂ red open circles, MgCl₂ blue crosses) and H atom in –OH headgroup of CHOL.

Figure 7

Isotherm of surface pressure (π) vs. area per molecule (MMA) of CHOL monolayers in a 15 mM subphase of monovalent salts (NaCl black open circles and NaI green open circles) (standard deviation <2%).

Figure 8

Isotherm of surface pressure (π) vs. area per molecule (MMA) of CHOL monolayers in a 5 mM subphase of MgCl₂ (blue crosses), CaCl₂ (red open circles) and in a 15 mM subphase of NaCl (black open circles) (standard deviation <2%).