Effect of sterol structure on molecular interactions and lateral domain formation in monolayers containing dipalmitoyl phosphatidylcholine.

Molecular associations between different sterols and dipalmitoyl phosphatidylcholine (DPPC) were examined in monolayers at the air/water interface. The sterols examined included cholesterol, 5-cholesten-3- one, 4-cholesten-3 beta-ol, 4-cholesten-3-one, cholesteryl acetate, and cholesteryl methyl-and ethyl ether. Information about the long-range order in pure sterol monolayers, as well as lateral domain-formation in mixed sterol/DPPC monolayers was obtained from the lateral miscibility or distribution of NBD-cholesterol (present at 0.5 mol%), as determined by monolayer epifluorescence microscopy. It was observed that the miscibility of NBD-cholesterol with the host sterol was limited in all monolayers except those of 5-cholesten-3-one and 4-cholesten-3-one, suggesting that only these monolayers lacked a long-range order present in the other sterol monolayers. Note that the term long-range order does not necessarily imply that the monolayer is solid. In mixed monolayers containing 3 beta-OH sterols and DPPC, cholesterol formed laterally condensed domains whereas 4-cholesten-3 beta-ol did not. This finding suggest that the sterols/DPPC interaction is sensitive to the position of the double-bond of the sterol molecule (delta 5 versus delta 4). Neither of the 3-keto sterols formed laterally condensed domains with DPPC. Cholesteryl acetate, however, formed lateral domains with DPPC which were in part similar to those seen in the cholesterol/DPPC system. The domains formed were circular, indicating their fluid nature. Mixed monolayers containing either of the ether sterol derivatives failed to produce clearly defined condensed domains with DPPC, although both mixed monolayers had a surface texture which suggested some degree of nonuniform distribution of the fluorescent probe. In summary, these novel results directly demonstrate the selective importance of both the delta 5 double bond, as well as of specific functional groups at the 3-position, for the molecular association with DPPC, and consequently for the formation of sterol/phospholipid-rich lateral domains.