Molecular Simulations of Ladderane Lipid Bilayers as Initial Models for Anammox Bacteria.

Ladderanes uniquely distinguish themselves from other lipids by possessing fused cyclobutane and cyclohexane rings down the length of their hydrocarbon tails. Found naturally only in anaerobic ammonium-oxidizing (anammox) bacteria and localized specifically to the anammoxosome, the compartmentalized site of anammox oxidation, the exact function and significance of ladderane containing phospholipids is still unclear. In this study, the all-atom CHARMM36 (C36) lipid force field is used to simulate two pure ladderane phosphatidylcholine bilayers, one containing only [3]-ladderane and the other containing both [3]- and [5]-ladderane. Values for surface areas per lipid (SA/lip), area compressibility, electron density profiles (EDPs), and bilayer thickness were calculated. While our measured values for area compressibility and EDPs are in line with previous simulation work involving ladderanes, our use of updated C36 protocols yielded a higher SA/lip and lower bilayer thickness, suggesting looser bilayer packing and less ordering of lipid tails than previously thought. We also report for the first time calculated values for order parameters, lipid wobble, interdigitation, and electrostatic potential for pure ladderane bilayers. The current model presents a baseline for future modeling of physiologically accurate anammox bacterial membranes and for studying of the function of ladderane lipids.