Lipid Monolayer Packing and Compressibility with Evolved Sterols

The quest for adequate formulations of liposomal carriers is a primary focus for drug delivery applications. Not only can it help develop more effective therapies, but it can also minimize side effects and create advanced drug delivery systems. Standard liposomal carriers are typically composed of lipids and cholesterol – the two primary building blocks of cell membranes. Here, we investigated how other sterols, such as 7-dehydrocholestrol (7-DHC) – a precursor to cholesterol, affect the structural organization and biophysical properties of lipid membranes. Our studies utilize Langmuir studies of lipid monolayers with varying concentrations of 7-DHC. Surface pressure-area isotherms recorded with continuous monolayer compression are used to obtain molecular packing. Our results show that as 7-DHC concentration increases up to ~30-40% mol%, the molecular area decreases monotonically, indicating tighter lipid packing and larger monolayer thickness. However, when benchmarked against cholesterol, our measurements indicate that 7-DHC is less effective than cholesterol in densifying lipid membranes. Our results highlight the concentration dependence of 7-DHC in regulating the physical properties of lipid monolayers. These observations demonstrate how alteration in sterol structure can impact unique biophysical properties that can be effectively utilized in liposomal applications.