Intermolecular interaction of phosphatidylinositol with the lipid raft molecules sphingomyelin and cholesterol

Diacylphosphatidylinositol (PI) is the starting reactant in the process of phosphatidylinositide-related signal transduction mediated through the lipid raft domain. We investigated intermolecular interactions of PI with major raft components, sphingomyelin (SM) and cholesterol (Chol), using surface pressure–molecular area (π–A) isotherm measurements. The classical mean molecular area versus composition plot showed that the measured mean molecular areas are smaller in PI/Chol mixed monolayers and larger in PI/SM mixed monolayers than those calculated on the basis of the ideal additivity. These results indicate that PI interacts attractively with Chol and repulsively with SM. In addition, we energetically evaluated the interaction of PI with SM/Chol mixtures and found that the mixing energy of PI/SM/Chol ternary monolayers decreased as the molar ratio of Chol to SM increased. In order to quantitatively analyze the distribution of PI we calculated the chemical potentials of mixing of PI into the SM/Chol mixed monolayer and into the dioleoylphosphatidylcholine (DOPC) monolayer, which was used as a model for the fluid matrix, on the basis of partial molecular area analysis. Analysis using the chemical potential of mixing of PI suggested that partition of PI molecules between these two monolayers can be changed by a factor of about 1.7 in response to change in Chol molar fraction in the SM/Chol mixed monolayer from 0.3 to 0.6 when the concentration of PI in the DOPC monolayer is kept constant at 7 mol%.