Dense yet flexible: how ladderanes found in anammox bacteria impact phospholipid membrane structure and properties

The composition of phospholipid membranes in cellular organelles is tailored to their functionality and reflects the evolutionary pressures prevailing in specific environmental niches. While many organisms share common membrane motifs, anaerobic ammonium-oxidising bacteria stand out as their membranes are enriched with distinctive ladder-like molecules called ladderanes. Membranes containing these conjugated cyclobutane structures have been studied for their permeation properties, density, and organisation, but their exact biological function remains unclear. In the present work, molecular dynamics simulations were used to investigate the behaviour of phospholipid membranes containing ladderane phospholipids or ladderane alcohols. The simulations showed that increased ladderane phospholipid content disrupted the membrane order and made it more permeable to hydrazine, while ladderane alcohols had a stabilising effect and maintained a well-ordered bilayer structure with low permeability. The results further indicate that compared to common phospholipid membranes, membranes bearing ladderane alcohols possess unusually high fluidity even at low environmental temperatures while retaining a high membrane density comparable to rigid membranes in the gelled state. This phase behaviour of membranes revealed surprising similarities between the roles of ladderane alcohols and cholesterol in terms of membrane fluidity and molecular order, providing a possible new angle on the biological role of these unusual ladder-like molecules in anammox bacteria.