Mapping the structure-activity relationship of β-sitosteryl fatty acid esters in condensing phospholipid monolayers

The phase behavior of twelve synthesized beta-sitosteryl fatty acid esters with acyl moieties with different chain lengths (C2: 0-C18: 0) and different degrees of unsaturation (C18: 1-C18: 3) were investigated in pure and mixed Langmuir monolayers with phospholipids. The surface-pressure isotherms showed that short chain beta-sitosteryl fatty acid esters gave smaller mean molecular areas and had decreased monolayer stability and the long chain steryl esters did not produce collapsed plateaus. All the steryl esters displayed strong condensing effects, but there was a pronounced structural dependency: medium chain esters (C8 and C10) were less efficient than short and long chain esters. Atomic force microscopy imaging demonstrated that monolayers mixed with dipalmitoyl phosphatidylcholine (DPPC) displayed both DPPC-rich and steryl lipid-rich domains. However, the height and area differences between the two phases and the roughness and morphologic patterns were very dependent on the steryl lipid concentrations as well as the length, the degree of unsaturation and the molecular conformations of the acyl segments. These findings not only provide a better understanding of the interactions between phytosteryl hydrophobic derivatives and biomembranes, but also may be of general use for the design and engineering of phytosterol structural derivations for specific food and pharmaceutical applications.