Cholesterol solubility in mixed DMPE/DMPC bilayers as determined by small angle X-ray scattering

Small angle X-ray scattering measurements under ambient conditions (T ≈ 294 K) provide evidence for the formation of separate domains in a ternary, mixed phospholipid ([DMPE]/[DMPC] = 3/1) / cholesterol model bilayer membrane. As we interpret these results, the domains contain cholesterol and DMPC, with which cholesterol is known to preferentially interact in a binary model membrane (solubility limit, mol fraction cholesterol 0.5), as compared to DMPE (solubility limit, mol fraction cholesterol 0.45). The solubility limit for the ternary system is mol fraction cholesterol 0.2–0.3. Although literature EPR spectra find that non-crystalline, cholesterol bilayer domains may be present even prior to the observation of cholesterol crystal diffraction, X-ray scattering cannot detect their presence.