Download (.pdf) Action of an Antiparasitic Peptide Active against African Sleeping Sickness in Biomembrane Models
Luciano Caseli, Cauê Piantandi Pascholati, Esteban Parra Lopera, Felippe J. Pavinatto, Thatyane M. Nobre, Maria Elisabette. D. Zaniquelli Claudius D'Silva, Tapani Viitala, Osvaldo N. Oliveira Jr. Biophysical Journal, (2010). Action of an Antiparasitic Peptide Active against African Sleeping Sickness in Biomembrane Models, 98(3 (1)), 627.
Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping Sickness, which have... more Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping Sickness, which have motivated the research into the ability of these compounds to disrupt the protozoan membrane. In this present study, we used the Langmuir monolayer technique to investigate the surface properties of an antiparasitic and zwitterionic peptide, namely S-(2,4-dinitrophenyl) glutathione di-2-propyl ester, and its interaction with a model membrane comprising a phospholipid monolayer, dipalmitoyl phosphatidyl choline (DPPC). The peptide formed a stable Langmuir monolayer, whose main feature of its surface pressure-area isotherm was the presence of a phase transition accompanied by a negative surface compressional modulus, which was attributed to the aggregation upon compression due to intermolecular bond associations of the molecules. This was inferred from surface pressure and surface potential isotherms, Brewster angle microscopy (BAM) images, Polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), and dynamic elasticity measurements by the pendant drop technique. When co-spread with dipalmitoyl phosphatidyl choline (DPPC), the drug affected both the surface pressure and the monolayer morphology, even at high surface pressures and with low amounts of the drug. The results were interpreted by assuming a repulsive, cooperative interaction between the drug and DPPC molecules. Such repulsive interaction and the large changes in fluidity arising from drug aggregation may be related to the disruption of the membrane, which is key for the parasite killing property.
The Lipid Composition of a Cell Membrane Model Modulates the Action of an Antiparasitic Peptide at the Air-Water Interface
Rondinelli D. Herculano1, Felippe J. Pavinatto, Luciano Caseli, Claudius D'Silva, Osvaldo N. Oliveira Jr.,. Biochimica et Biophysica Acta, (2011), 1808 (7), 1907-1912.
The antiparasitic property of peptides is believed to be associated with their interactions with the protozoan... more The antiparasitic property of peptides is believed to be associated with their interactions with the protozoan membrane, which calls for research on the identification of membrane sites capable of peptide binding. In this study we investigated the interaction of a lipophilic glutathioine peptide known to be effective against the African Sleeping Sickness (ASS — African Trypanosomiasis) and cell membrane models represented by Langmuir monolayers. It is shown that even small amounts of the peptide affect the monolayers of some phospholipids and other lipids, which points to a significant interaction. The latter did not depend on the electrical charge of the monolayer-forming molecules but the peptide action was particularly distinctive for cholesterol + sphingomyelin monolayers that roughly resemble rafts on a cell membrane. Using in situ polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), we found that the orientation of the peptide is affected by the phospholipids and dioctadecyldimethylammonium bromide (DODAB), but not in monolayers comprising cholesterol + sphingomyelin. In this mixed monolayer resembling rafts, the peptide still interacts and has some induced order, probably because the peptide molecules are fitted together into a compact monolayer. Therefore, the lipid composition of the monolayer modulates the interaction with the lipophilic glutathioine peptide, and this may have important implications in understanding how the peptide acts on specific sites of the protozoan membrane.
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Solid-State 2H NMR Shows Equivalence of Dehydration and Osmotic Pressures in Lipid Membrane Deformation
by Mallikarjunaiah Kodirampura Jayaramappa
Published in Biophysical Journal
Lipid bilayers represent a fascinating class of biomaterials whose properties are altered by changes in pressure or... more Lipid bilayers represent a fascinating class of biomaterials whose properties are altered by changes in pressure or temperature. Functions of cellular membranes can be affected by nonspecific lipid-protein interactions that depend on bilayer material properties. Here we address the changes in lipid bilayer structure induced by external pressure. Solid-state 2H NMR spectroscopy of phospholipid bilayers under osmotic stress allows structural fluctuations and deformation of membranes to be investigated. We highlight the results from NMR experiments utilizing pressure-based force techniques that control membrane structure and tension. Our 2H NMR results using both dehydration pressure (low water activity) and osmotic pressure (poly(ethylene glycol) as osmolyte) show that the segmental order parameters (SCD) of DMPC approach very large values of ≈0.35 in the liquid-crystalline state. The two stresses are thermodynamically equivalent, because the change in chemical potential when transferring water from the interlamellar space to the bulk water phase corresponds to the induced pressure. This theoretical equivalence is experimentally revealed by considering the solid-state 2H NMR spectrometer as a virtual osmometer. Moreover, we extend this approach to include the correspondence between osmotic pressure and hydrostatic pressure. Our results establish the magnitude of the pressures that lead to significant bilayer deformation including changes in area per lipid and volumetric bilayer thickness. We find that appreciable bilayer structural changes occur with osmotic pressures in the range of 10−100 atm or lower. This research demonstrates the applicability of solid-state 2H NMR spectroscopy together with bilayer stress techniques for investigating the mechanism of pressure sensitivity of membrane proteins.