Insights into the role of cyclic ladderane lipids in bacteria from computer simulations

• Molecular dynamics simulations of ladderane (ladders of cyclic aliphatic rings) containing bilayers are reported.
• Hydrazine penetrates the ladderane bilayer more readily than POPC bilayer.
• Inclusion of ladderane moieties increases the density and area compressibility modulus of the bilayer.

Ladderanes, which are multiple fused cyclobutane rings, are unique structures available only in nature. Anammox bacteria produce ladderane phospholipids during their life cycle, but the synthesis mechanism still remains a mystery. The function of ladderane lipids in the membrane is unclear as well. According to previous speculations, ladderane moieties of the bilayer might decrease permeability for certain molecules, which should not diffuse out of the compartment enclosed by the ladderane-containing membrane. We report the first atomistic-precision molecular dynamics simulations of bilayers containing ladderane lipids. The structural and thermodynamics differences among (1) pure ladderane containing bilayer, (2) POPC bilayer, and (3) their equimolar mixture are discussed. Potentials of mean force are reported for the translocation of a hydrazine molecule through all investigated bilayers. All bilayers offer a potential energy barrier to hydrazine. Contrary to expectations, the presence of the ladderane lipids somewhat lowers the barrier for translocation of hydrazine. We conclude that the presence of ladderane phospholipids in anammox bacteria does not serve as a barrier to hydrazine. It may serve as a barrier to larger and noxious intermediates in the anammox reaction, or, the true mission of ladderane lipids must be located in a different plane.