The Effect of Sterol Side Chain Conformation on Lateral Lipid Domain Formation in Monolayer Membranes

Abstract

The unique structure of cholesterol appears to have evolved to give the molecule important functions and properties as a membrane component. The amphiphilic properties of cholesterol are provided by the hydrophilic 3P-hydroxy group, the hydrophobic tetracyclic ring structure, and the isooctyl side chain at position C-17. The side chain seems to be important for proper interactions with phospholipids in membranes [Demel et al. , 1972a; Demel et al. , 1972b]. 5-Androsten-3P-ol, which lacks the isooctyl side chain, can neither condense dipalmitoylphosphatidylcholine (DPPC) monolayers [Demel et al. 1972a; Slotte et al. , 1994], nor reduce the solute permeability of phosphatidylcholine liposomes [Nakamura et al. , 1980]. Sterols having shorter or longer side chains, as compared to the isooctyl chain of cholesterol, are also less effective as rigidifiers in phospholipid bilayer membranes than cholesterol [Suckling & Boyd, 1976; Craig et al. , 1978; Suckling et al. , 1979]. A study from our laboratory using cholesterol oxidase as a probe for the strength of sterol-phospholipid interaction also reported a significant difference in sterol/phospholipid interaction in both small unilamellar vesicles and monolayers as a function of the sterol side chain composition [Slotte et al. , 1994].