Outer layer of cellular membrane contains ordered domains enriched in cholesterol and sphingolipids, called ‘lipid rafts’, which play various biological roles, i.e. they are involved in the induction of cell death by apoptosis. Recent studies have shown that these domains may constitute binding sites for some drugs. Some of them are alkylphosphocholines (APC). The mode of action of APC, which are new generation antitumor agents characterized by high selectivity and broad spectrum of activity, has been hypothesized to be linked with the alternation of biophysicals properties of lipid rafts. To get a deeper insight into this issue, interactions between selected APCs (miltefosine and erucylphosphocholine) and a raft model (composed of cholesterol and sphingomyelin mixed in 1:2 proportion) were investigated using the Langmuir monolayer technique.
The obtained results, based on experimental π – A isotherms complemented with visualization method (Brewster angle microscopy), confirm the alteration in physical parameters of raft membrane by APCs. Namely, drug molecules induce a phase separation and fluidize the model raft system.
anita.wnetrzak@uj.edu.pl
