Structural Interpretation of the Large Slowdown of Water Dynamics at Stacked Phospholipid Membranes for Decreasing Hydration Level: All-Atom Molecular Dynamics

Abstract

Hydration water determines the stability and function of phospholipid membranes as well as the interaction of membranes with other molecules. Experiments and simulations have shown that water dynamics slows down dramatically as the hydration decreases, suggesting that the interfacial water that dominates the average dynamics at low hydration is slower than water away from the membrane. Here, based on all-atom molecular dynamics simulations, we provide an interpretation of the slowdown of interfacial water in terms of the structure and dynamics of water-water and water-lipid hydrogen bonds (HBs). We calculate the rotational and translational slowdown of the dynamics of water confined in stacked phospholipid membranes at different levels of hydration, from completely hydrated to poorly hydrated membranes. For all hydrations, we analyze the distribution of HBs and find that water-lipids HBs last longer than water-water HBs and that at low hydration most of the water is in the interior of the membrane. We also show that water-water HBs become more persistent as the hydration is lowered. We attribute this effect (i) to HBs between water molecules that form, in turn, persistent HBs with lipids; (ii) to the hindering of the H-bonding switching between water molecules due to the lower water density at the interface; and (iii) to the higher probability of water-lipid HBs as the hydration decreases. Our interpretation of the large dynamic slowdown in water under dehydration is potentially relevant in understanding membrane biophysics at different hydration levels.

Keywords: confinement; diffusion; molecular dynamics; phospholipid membrane; water.

Figure 1

Snapshots of the six systems considered in our study, with hydration levels (a) 34; (b) 20; (c) 15; (d) 10; (e) 7; and (f) 4. Gray and red beads represent phospholipid tails and headgroups, respectively. Blue and white beads represent oxygen and hydrogen atoms of water. The dashed line indicates the size of the simulation box.

Figure 1

Snapshots of the six systems considered in our study, with hydration levels (a) 34; (b) 20; (c) 15; (d) 10; (e) 7; and (f) 4. Gray and red beads represent phospholipid tails and headgroups, respectively. Blue and white beads represent oxygen and hydrogen atoms of water. The dashed line indicates the size of the simulation box.

Figure 2

Translational dynamics of confined water molecules projected on the plane of the membrane for the different stacked phospholipid bilayers. (a) mean-square displacement on the plane of the membrane (MSD${}_{\parallel }$) as a function of time; (b) diffusion coefficient of water molecules on the plane of the membrane for the different hydration levels considered.

Figure 3

(a) rotational dipolar correlation function of water molecules calculated from simulations of DMPC phospholipid bilayers with different levels of hydration ω; (b) the partition of all the water in the system into the fractions (i) $f_{\mathrm{bulk}}$ of bulk-like (lower circles); (ii) $f_{\mathrm{irr}}$ of irrotational (upper circles) and (iii) $f_{\mathrm{fast}}=1-f_{\mathrm{bulk}}-f_{\mathrm{irr}}$ of fast water molecules, as a function of the hydration level ω in Equation (5), following the decomposition of the rotational correlation function proposed in Ref. [10]. The dots represent the partitioning from MD simulations. Full lines are guides for the eyes.

Figure 4

Changes in HB structure with hydration level ω. (a) average number $\langle n_{HB}\rangle$ of total HBs formed by each water molecule confined in stacked phospholipid membranes; (b) fraction of HBs between water molecules and lipid groups.

Figure 5

Normalized distributions of the number of HBs per water molecule in stacked membranes for (a) $\omega =34$; (b) $\omega =10$; and (c) $\omega =4$. At each hydration level, we present the normalized distribution of water molecules forming a given number of HBs ≤5 with other water molecules (left), with lipid groups (center), and the normalized distribution of the sum of the two kinds of HBs (right).

Figure 5

Normalized distributions of the number of HBs per water molecule in stacked membranes for (a) $\omega =34$; (b) $\omega =10$; and (c) $\omega =4$. At each hydration level, we present the normalized distribution of water molecules forming a given number of HBs ≤5 with other water molecules (left), with lipid groups (center), and the normalized distribution of the sum of the two kinds of HBs (right).

Figure 6

Fraction of water molecules forming $n_{\mathrm{wat}}$ HBs with other water molecules, and, at the same time, $n_{\mathrm{lip}}$ HBs with lipids, indicated along the x-axis as $(n_{\mathrm{wat}},n_{\mathrm{lip}})$, for different hydration levels. At high hydration ($\omega =34$, blue circles) the HBs are mainly among water molecules. At medium hydration ($\omega =10$, green triangles) the most likely structures have $n_{\mathrm{wat}}=2$ and $n_{\mathrm{lip}}=1$, but still many water molecules have no HBs with lipids. At low hydration ($\omega =4$, red squares), in general, the water HBs are involving at least one lipid and one or two more water molecules.

Figure 7

Relaxation of the time correlation functions $C_{HB}^{w-w}\left(t\right)$ (a) and $C_{HB}^{w-l}\left(t\right)$ (b) for stacked phospholipid membranes with hydration levels $\omega =4$ (black circles), $\omega =7$ (blue squares), $\omega =10$ (cyan triangles down), $\omega =15$ (green triangles up), $\omega =20$ (pink pentagons), $\omega =34$ (red hexagons).

Figure 8

Density of water molecules confined between stacked DMPC bilayers with hydration level $\omega =4$, 7, 15, 34, as a function of the membrane distance ξ with respect to one of the two confining membranes. We define three relevant regions: (i) interior of the membrane, with $\xi <0$; (ii) first hydration layer, with $0<\xi <5$ Å; (iii) exterior of the membrane, with $\xi >5$ Å.