Effects of cyclosporine A on biomembranes. Vibrational spectroscopic, calorimetric and hemolysis studies.
Cyclosporine A (CSA)-dipalmitoylphosphatidylcholine (DPPC) interactions were investigated using scanning calorimetry, infrared spectroscopy, and Raman spectroscopy. CSA reduced both the temperature and the maximum heat capacity of the lipid bilayer gel-to-liquid crystalline phase transition; the relationship between the shift in transition temperature and CSA concentration indicates that the peptide does not partition ideally between DPPC gel and liquid crystalline phases. This nonideality can be accounted for by excluded volume interactions between peptide molecules. CSA exhibited a similar but much more pronounced effect on the pretransition; at concentrations of 1 mol % CSA the amplitude of the pretransition was less than 20% of its value in the pure lipid. Raman spectroscopy confirmed that the effects of CSA on the phase transitions are not accompanied by major structural alterations in either the lipid headgroup or acyl chain regions at temperatures away from the phase changes. Both infrared and Raman spectroscopic results demonstrated that CSA in the lipid bilayer exists largely in a beta-turn conformation, as expected from single crystal x-ray data; the lipid phase transition does not induce structural alterations in CSA. Although the polypeptide significantly affects DPPC model membrane bilayers, CSA neither inhibited hypotonic hemolysis nor caused erythrocyte hemolysis, in contrast to many chemical agents that are believed to act through membrane-mediated pathways. Thus, agents, such as CSA, that perturb phospholipid phase transitions do not necessarily cause functional changes in cell membranes.
D002152:Calorimetry, Differential Scanning / Q000379:methods; D003524:Cyclosporins / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D011663:Pulmonary Surfactants; D013055:Spectrophotometry, Infrared / Q000379:methods; D013059:Spectrum Analysis, Raman / Q000379:methods; D014732:Vibration
D003524:Cyclosporins; D008081:Liposomes; D011663:Pulmonary Surfactants