Biophysical Effects of Cholesterol on Packing and Elasticity of Lipid Membranes*

The stabilization of liposomal carriers capable of delivering drugs into the body is a topic of utmost priority. Carriers made of lipids – the building blocks of our cell membranes – are an ideal candidate due to their biocompatibility. However, major challenges still exist in achieving optimal liposomal stability and prolonged circulation. This study focuses on the effects of cholesterol as a liposomal stabilizer. To test these effects, we utilize Langmuir monolayer measurements of lipid and cholesterol mixtures, which allow direct observations of cholesterol effects on lipid packing and the area compressibility modulus within the monolayer. Our measurements, performed with varying amounts of cholesterol, demonstrate that increasing cholesterol content leads to tighter lipid packing, as expected. What is more, calculations of the area compressibility modulus and the Gibbs free energy reveal increasing monolayer stiffness and favorable interactions with cholesterol concentrations up to ~ 50 mol%. Combined with data from neutron spectroscopy measurements on corresponding liposomal membranes, these studies demonstrate the molecular and interaction mechanisms underlying cholesterol-induced stabilization of lipid membranes.