Specific adsorption of pla(2) at monolayers.

Specific phospholipase A2 (PLA2) adsorption studies were performed on monolayers of d-dipalmitoyl-phosphatidylcholine (d-DPPC) and of an ether-ester d-1-O-hexadecyl-2-stearoyl-phosphatidylcholine (d-HSPC). In order to separate interfacial recognition from subsequent lipid cleavage, PLA2-resistant d-enantiomers were utilized for the investigations. Snake venom (N. naja naja and Crotalos atrox) PLA2, which hydrolyzes the sn-2 ester bond of l-phospholipids, was used. Fluorescence microscopy, film-balance pressure–area isotherms, and grazing incidence X-ray diffraction (GIXD) experiments were carried out. Fluorescence microscopy studies show that the enzyme accumulates preferentially at the liquid-expanded/condensed interface. At low surface pressure enzyme penetration into the monolayer is observed, whereas at high pressures the area per molecule is reduced upon specific adsorption. Monolayer structure, as determined by GIXD, is greatly affected by adsorption of PLA2. The tilt angle of the aliphatic chains of the monolayer becomes drastically reduced due to an enzyme-induced increase of the lipid packing efficiency. The unspecific adsorption of serum albumin to a d-DPPC monolayer does not change the monolayer structure. The structural changes, caused by PLA2 adsorption on d-enantiomer monolayers, are related to the chemical structure of the lipid molecules. Therefore, a relation between structure change and hydrolysis efficiency of PLA2 on the respective l-enantiomer monolayers can be assumed

Binding of Nonsteroidal Anti-inflammatory Drugs to DPPC: Structure and Thermodynamic Aspects

The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the phase transition and phase properties of 1,2-dipalmitoylphosphatidylcholine (DPPC) has been investigated in both 2D (monolayers at the air/water interface) and 3D (multilayers in lipid/water dispersions) model systems. The 2D membrane models have been characterized by means of pressure-area isotherms and grazing incidence X-ray diffraction (GIXD) measurements. Differential scanning calorimetry (DSC) and simultaneous small- and wide-angle X-ray diffraction have been applied to lipid aqueous dispersions. All NSAIDs studied altered the main transition temperature of the gel to liquid-crystalline phase transition, with the arylacetic acid derivatives (acemetacin and indomethacin) showing the largest effects. A comparison of the results reveals distinct structural features of the membrane models after interaction with the NSAID. All drugs induced perturbations in the lipid liquid-crystalline phase, suggesting a major change in the hydration behavior of DPPC. Again, the largest effects on the structural parameters are found for the arylacetic acid derivatives. The results obtained in the different model systems give indications of the role of the membrane/NSAID interactions that might also be important for NSAID gastric injury