Evidence for capture of spin-labeled ibuprofen drug molecules by lipid rafts in model membranes.

Lipid rafts are lipid-cholesterol nanostructures thought to exist in cell membranes, which are characterized by higher ordering compared to their surroundings. Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) have a high affinity for phospholipid membranes and can alter their structure and biological properties. Here we use electron paramagnetic resonance (EPR) in its pulsed electron spin echo (ESE) version to study spin-labeled ibuprofen (ibuprofen-SL) in a raft-mimicking bilayer, which consists of an equimolar mixture of the phospholipids dioleoyl-glycero-phosphocholine (DOPC) and dipalmitoyl-glycero-phosphocholine (DPPC), with cholesterol added in various proportions. ESE decays are sensitive to the presence of low-temperature small-angle orientational motions of molecules - stochastic molecular librations. The data obtained show that in the presence of lipid rafts the temperature dependence of the spin relaxation rate induced by this motion reaches a plateau. This behavior is characteristic of non-cooperative motion of a molecule bound to some structure denser than the rest of the medium. Based on this analogy, the data obtained were interpreted as evidence that ibuprofen-SL molecules are adsorbed on the raft boundaries.