How alcohol chain-length and concentration modulate hydrogen bond formation in a lipid bilayer

Abstract

Molecular dynamics simulations are used to measure the change in properties of a hydrated dipalmitoylphosphatidylcholine bilayer when solvated with ethanol, propanol, and butanol solutions. There are eight oxygen atoms in dipalmitoylphosphatidylcholine that serve as hydrogen bond acceptors, and two of the oxygen atoms participate in hydrogen bonds that exist for significantly longer time spans than the hydrogen bonds at the other six oxygen atoms for the ethanol and propanol simulations. We conclude that this is caused by the lipid head group conformation, where the two favored hydrogen-bonding sites are partially protected between the head group choline and the sn-2 carbonyl oxygen. We find that the concentration of the alcohol in the ethanol and propanol simulations does not have a significant influence on the locations of the alcohol/lipid hydrogen bonds, whereas the concentration does impact the locations of the butanol/lipid hydrogen bonds. The concentration is important for all three alcohol types when the lipid chain order is examined, where, with the exception of the high-concentration butanol simulation, the alcohol molecules having the longest hydrogen-bonding relaxation times at the favored carbonyl oxygen acceptor sites also have the largest order in the upper chain region. The lipid behavior in the high-concentration butanol simulation differs significantly from that of the other alcohol concentrations in the order parameter, head group rotational relaxation time, and alcohol/lipid hydrogen-bonding location and relaxation time. This appears to be the result of the system being very near to a phase transition, and one occurrence of lipid flip-flop is seen at this concentration.

FIGURE 1

Structure of DPPC (hydrogen atoms are not included).

FIGURE 2

The DPPC area per lipid for the control and six alcohol simulations during the data collection phase. The control, ethanol, and propanol simulations have a 2-fs time step, and the butanol simulations have a 1-fs time step.

FIGURE 3

Density profiles for the low-concentration propanol solution for DPPC (solid line), the DPPC nitrogen atom (dotted line), the DPPC glycerol oxygen (heavy solid line), propanol (dashed line), and water (lightly dotted line). Density profiles have been centered at 3.3 nm.

FIGURE 4

Density profiles for DPPC in an alcohol-free environment and with two ethanol solutions. Density profiles have been centered at 3.3 nm.

FIGURE 5

The first nitrogen (N)-OB rdf peak height is larger than that of N-OC. Likewise, the first N-OF rdf peak height is greater than that of N-OH. The rdf values in this figure are averaged over the ethanol, propanol, and low-butanol-concentration simulations (these five concentrations show the same trends when examined individually).

FIGURE 6

An example of a DPPC lipid whose head group conformation partially encloses hydrogen bond acceptors OB and OF.

FIGURE 7

Number of hydrogen bonds (%) that form at the phosphate oxygen acceptors (OA–OD), the glycerol oxygen acceptors (OE, OG), and the upper chain carbonyl oxygen acceptors (OF, OH). On the x axis, the alcohol concentrations are labeled as E for the ethanol solutions, P for the propanol solutions, and B for the butanol solutions.

FIGURE 8

Order parameter profiles for the DPPC sn-2 chains.

FIGURE 9

DPPC phosphorus atom density profile for one leaflet. The bilayer is centered at 3.3 nm.

FIGURE 10

The z-axis coordinates of the lipid that flip–flops as it traverses the bilayer. The lipid is closely aligned with a butanol molecule when it is located in the center of the bilayer (3.3 nm).

FIGURE 11

A snapshot of the lipid in transit from the bottom leaflet to the top leaflet. While located in the center of the bilayer, the lipid partners with a butanol molecule (blue molecule).