Mixed bilayer containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine: lipid complexation, ion binding, and electrostatics

Abstract

Two mixed bilayers containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine at a ratio of 5:1 are simulated in NaCl electrolyte solutions of different concentration using the molecular dynamics technique. Direct NH.O and CH.O hydrogen bonding between lipids was observed to serve as the basis of interlipid complexation. It is deduced from our results and previous studies that dipalmitoylphosphatidylcholine alone is less likely to form interlipid complexes than in the presence of bound ions or other bilayer "impurities" such as dipalmitoylphosphatidylserine. The binding of counterions is observed and quantitated. Based upon the calculated ion binding constants, the Gouy-Chapman surface potential (theta) is calculated. In addition we calculated the electrostatic potential profile (Phi) by twice integrating the system charge distribution. A large discrepancy between and the value of Phi at the membrane surface is observed. However, at "larger" distance from the bilayer surface, a qualitative similarity in the z-profiles of Phi and psi(GC) is seen. The discrepancy between the two potential profiles near the bilayer surface is attributed to the discrete and nonbulk-like nature of water in the interfacial region and to the complex geometry of this region.

FIGURE 1

Structures of the simulated DPPS (PS) and DPPC (PC) molecules. The atom naming is adopted from a previous convention (Smondyrev and Berkowitz, 1999).

FIGURE 2

Time series data of the centers of mass of the ions in both systems.

FIGURE 3

Distribution of the angle between (the vector pointing from the headgroup phosphorus atom to the headgroup nitrogen atom) and the outwardly directed bilayer normal for each lipid in both systems.

FIGURE 4

Schematic diagram showing the established criteria for NH···O and CH···O hydrogen bonding.

FIGURE 5

Distribution of the number of lipids bound to a given lipid via direct bonding for each PC and PS in both systems.

FIGURE 6

Distribution of the number of lipids bound to a given lipid via direct bonding in a pure DPPC system with and without salt.

FIGURE 7

Distribution of different types of direct hydrogen bonding for “smaller” and “larger” lipid complexes for both lipid types in both simulated systems.

FIGURE 8

Snapshots showing complexation of lipids. A schematic representation of each complex is also shown. In the representations, blue arrows represent PS, black arrows represent PC, and red lines represent the interlipid direct hydrogen bonds. The arrowheads correspond to the nitrogen atom of the headgroup.

FIGURE 9

Distribution of the number of lipids bound to a single cation for both cation species in both systems.

FIGURE 10

Snapshots of complexes involving an ion bridge. Na⁺ (blue sphere) is coordinated with two PC lipids and two PS lipids (left). is coordinated with four lipids via hydrogen bonds (right).

FIGURE 11

Various quantities as a function of z in the S₂ system: (a) hydration level of each ion type, (b) densities of various atom types, and (c) number of ions of each type.

FIGURE 12

Various quantities as a function of z in the S₁ system: (a) hydration level of each ion type, (b) densities of various atom types, and (c) number of ions of each type.

FIGURE 13

(a) Total electrostatic potential profile of the S₂ system as a function of z. (b) Density profile of co- and counterions as a function of z in the S₂ system.

FIGURE 14

(a) Total electrostatic potential profile of the S₁ system as a function of z. (b) Density profile of co- and counterions as a function of z in the S₁ system.