Cyclosporin A in membrane lipids environment : implications for antimalarial activity of the drug : the Langmuir monolayer studies

Cyclosporin A (CsA), a hydrophobic cyclic peptide produced by the fungus Tolypocladium inflatum, is well known for its high efficiency as an immunosuppressor for transplanted organs and anti-inflammatory properties; however, it is also active as antiparasitic (antimalarial) drug. Antimalarial mechanism of CsA action lacks a detailed understanding at molecular level. Due to a high lipophilicity of CsA, it is able to interact with lipids of cellular membrane; however, molecular targets of this drug are still unknown. To get a deeper insight into the mode of antimalarial activity of CsA, it is of utmost importance to examine its interactions with membrane components. To reach this goal, the Langmuir monolayer technique, which serves as a very useful, easy to handle and controllable model of biomembranes, has been employed. In this work, the interactions between CsA and main membrane lipids, i.e., cholesterol (Chol), 2-oleoyl-1-palmitoyl-3-phosphocholine (POPC), and sphingomyelin (SM), have been investigated. Attractive interactions are observed only for CsA mixtures with SM, while repulsive forces occur in systems containing remaining membrane lipids. Taking into consideration mutual interactions between membrane lipids (Chol–SM; Chol–POPC and SM–POPC), the behavior of CsA in model erythrocyte membrane of normal and infected cells has been analyzed. Our results prove strong affinity of CsA to SM in membrane environment. Since normal and parasitized erythrocytes differ significantly in the level of SM, this phospholipid may be considered as a molecular target for antimalarial activity of CsA

Properties of DNA-CTMA monolayers obtained by Langmuir-Blodgett technique

The complex consisting of DNA and cetyltrimethylammonium chloride (DNA-CTMA) is extensively exploited in organic electronics in form of thin films with submicron or nanometer thickness. In this work, using the Langmuir-Blodgett technique, the surface films were prepared from complexes based on different types of chromosomal and plasmid DNA. The research focused on changes in their continuity after they were transferred onto a solid substrate. It was found that only the monolayer of plasmid DNA-CTMA complex remained continuous after being transferred. The other complexes underwent a spontaneous self-assembling and created elongated linear patterns. AFM images of these patterns were analysed quantitatively with Fast Fourier Transform. It was confirmed that self-assembling occurred along one privileged direction