Investigating structure-property relations in cholesterol-rich lipid membranes.

Cholesterol is a key molecule in eukaryotic cell membranes. It mediates essential membrane processes, including viral budding and the mechanical resistance of membranes against pathogens. Hence, understanding the influence of cholesterol on the mechanics of functional membranes is crucial. Cholesterol is known to cause lipids to pack more tightly, manifesting in a decrease in the average area per lipid, AL, at the aqueous interface. Yet, how variations in packing density influence the elastic properties of lipid membranes with varying degrees of chain unsaturation remains largely unexplored. Theories based on mean field calculations have predicted various forms of the interdependence between the bending rigidity modulus, κ, and lipid packing density. However, direct assessments of these predictions have been limited, due to the difficulty in accessing the membrane's mechanical properties on the nanoscale. To address this, we performed studies using neutron spin-echo spectroscopy, solid-state 2H NMR relaxometry, and molecular dynamics simulations on lipid membranes with different degrees of chain unsaturation. We find that cholesterol has a stiffening effect on all studied membranes over the accessible length and time scales. Our findings show that κ has an inverse dependence on AL, indicating that cholesterol controls membrane elastic properties by modifying lipid packing density. As AL decreases, the number of conformations accessible to the lipid chains also decreases and the membrane becomes more rigid. Yet, different expressions of κ vs. AL are obtained when we consider reduced variables. Establishing well-defined structure-property relationships will open up new possibilities for predicting the behavior of more complex biological membranes and will inform design rules for engineered membranes and artificial cells with real-world functionalities.