Understanding Ladderane Lipid Packing in Anammox Bacterial Membranes

Eukaryotic membranes typically contain saturated and unsaturated fatty acyl chains, while microbial membranes often incorporate aliphatic rings to enhance stability and fluidity under adverse conditions. Anammox bacteria, which convert ammonium and nitrite/nitrate into N₂ gas anaerobically, possess unique ladderane lipids with concatenated cyclobutane rings in their anammoxosome membranes, which are essential for their stability and function. Using density functional theory and molecular dynamics simulations, we optimize and analyze the interactions of two types of ladderane lipids ([3][3]LA and [5][3]LA) and compare them to those of conventional lipids (DMPC and POPC) in various environments. The results reveal strong London dispersion interactions within the ladderane hydrocarbon chains, contributing to dense packing and reduced lateral diffusion in mixed POPC-ladderane membranes. These findings suggest that ladderane lipids play a crucial role in maintaining membrane integrity and stability, potentially impacting molecular permeation and diffusion processes. The study provides insights into the biophysical properties of ladderane-containing membranes, highlighting their unique structural characteristics and interaction dynamics.