X-ray insight into cholesterol-phospholipid interactions

The mechanism of nonideal cholesterol-lipids mixing yet remains controversial. We report on a systematic study of cholesterol-phospholipid interactions in lipid monolayers using Langmuir isotherms, synchrotron X-ray reflectivity (XR), and grazing-incidence X-ray diffraction (GIXD) techniques. Lipid monolayers consisted of cholesterol-DPPC mixtures with cholesterol mole fractions $\chi _{CHOL}$ varying from 0 to 1. GIXD reveals that at both $\chi _{CHOL}$ and $\chi _{DPPC}$ above .85 mixed films exhibit packing order of a prevalent lipid. In between, cholesterol seizes places in DPPC crystalline lattice at the stoichiometry similar as that of the mixture inducing short-range regular-hexagonal packing order with increasing spacing between molecules as a function of cholesterol content. XR shows that cholesterol tends to stay in DPPC acyl chains at low $\chi _{CHOL}$ while gradually descending to a subphase at higher $\chi _{CHOL}$ accompanied by rearrangement of DPPC headgroups. Thus, a desire of highly nonpolar cholesterol to avoid contacts with polar water molecules and/or DPPC headgroups defines a mode of cholesterol-lipid interactions.