Molecular dynamics study of bipolar tetraether lipid membranes

Abstract

Membranes composed of bipolar tetraether lipids have been studied by a series of 25-ns molecular dynamics simulations to understand the microscopic structure and dynamics as well as membrane area elasticity. By comparing macrocyclic and acyclic tetraether and diether archaeal lipids, the effect of tail linkage of the two phytanyl-chained lipids on the membrane properties is elucidated. Tetraether lipids show smaller molecular area and lateral mobility. For the latter, calculated diffusion coefficients are indeed one order-of-magnitude smaller than that of the diether lipid. These two tetraether membranes are alike in many physical properties except for membrane area elasticity. The macrocyclic tetraether membrane shows a higher elastic area expansion modulus than its acyclic counterpart by a factor of three. Free energy profiles of a water molecule crossing the membranes show no major difference in barrier height; however, a significant difference is observed near the membrane center due to the lack of the slip-plane in tetraether membranes.

FIGURE 1

Chemical structures of 1,2-di-O-phytanyl-sn-glycero-3-phosphocholine (diphytanyl phosphatidylcholine, DPhPC), 1,2′-O-biphytanyl-1′,2-di-O-phytanyl-sn-diglycero-3,3′-bisphosphocholine (acyclic tetraether phosphatidylcholine, a-TEPC), and tetra-O-di(biphytanyl)-sn-diglycero-3,3′-bisphosphocholine (macrocyclic tetraether phosphatidylcholine, m-TEPC). The ether linkages in the glycerol backbones of these lipids were consistently set in an sn-1,2 configuration to compare MD simulation results for these lipids with those in previous articles (–16), whereas natural archaeal lipids are characterized by an exceptional sn-2,3 configuration.

FIGURE 2

(a) Time evolution of the averaged molecular area and (b) its probability distribution. (Dashed lines, DPhPC; shaded lines, a-TEPC; and solid lines, m-TEPC.)

FIGURE 3

Electron density profiles along the membrane normal, z. The center of the membrane core is taken at z = 0.

FIGURE 4

(a) Deuterium order parameter, S_CD, and (b) probability of gauche conformers as a function of carbon number in the hydrophobic chains. The carbon number denotes the segmental number counting from ether-linkage along the hydrophobic main chain. (Dashed lines, DPhPC; solid lines, m-TEPC; and shaded and shaded dashed lines, biphytanyl and phytanyl chains of a-TEPC, respectively. The arrows in b denote the positions of branching carbons.)

FIGURE 5

Snapshots (20 Å slab) of the membrane systems during the MD simulation. (a) DPhPC, (b) a-TEPC, and (c) m-TEPC. Phosphorus atoms are yellow, nitrogens are blue, oxygens are red, carbons are green, and hydrogens are white. Atoms in several selected lipid molecules are represented by spheres to show typical lipid conformations clearly.

FIGURE 6

Free-energy profiles of a water molecule across the membranes. (Dashed lines, DPhPC; shaded lines, a-TEPC; and solid lines, m-TEPC.) The center of the membrane core is taken at z = 0.

FIGURE 7

Twenty-five-nanosecond trajectories of lipid centers-of-mass (COM) on the membrane plane. (a) DPhPC, (b) a-TEPC, and (c) m-TEPC. The lines connecting the COM positions are calculated every 10 ps. For DPhPC, trajectories of the lipids in the upper leaflet are plotted.

FIGURE 8

Mean-square displacements of lipid COM in the membrane plane. Error bars represent the maximum and minimum values among three individual statistics by splitting trajectory into increments of 8.33 ns.

FIGURE 9

Mean-square displacements of (a) phosphorus and (b) C15 atoms. Error bars represent the maximum and minimum values among five individual statistics by splitting trajectory into increments of 5 ns.