ISSN:
1432-1017
Keywords:
2H-NMR
;
filipin
;
DMPC
;
circular dichroism
;
model membranes
;
carboxyfluorescein release
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Physics
Notes:
Abstract Interaction of the pentene antibiotic filipin with dimyristoylphosphatidylcholine (DMPC) membranes has been monitored by 2H-NMR, circular dichroism (CD), electronic absorption and fluorescence in the temperature range 10° to 60°C. Interaction appears to depend on whether filipin is added before or after membrane formation and also upon the temperature of the system. When filipin is added to preformed DMPC large unilamellar vesicles (LUV), the association constants, as determined by electronic absorption are 39×103 M -1, 15×103 M -1 and 0.6×103 M -1 at 15°, 30° and 50°C, respectively. Under identical conditions, CD spectra of bound filipin exhibit features characteristic of an aggregation over the whole temperature range. When filipin is incorporated in membranes during their preparation, the 2H-NMR spectra of deuterated DMPC indicate that the drug has a slight disordering effect on the lipid matrix below the temperature, T c ,of the gel-to-fluid phase transition and above T c +11°C. Between these two temperature boundaries the system consists of two lipid regions of very different dynamic properties. One of the regions, which is attributed to a filipin-lipid complex, has the properties of gel-like lipids whereas the other has those of fluid-like lipids. The latter domain is however more ordered than the pure lipid at corresponding temperatures. CD spectra under the same conditions are found to be identical to spectra when the drug is added to preformed membranes, only in the region T c to T c +11°C. Filipin induced carboxyfluorescein release from DMPC-LUV is found to be complete when the filipin-to-lipid ratio is near 1, for temperatures below T c +11°C. Results are compared to previous data on amphotericin B and provide evidence that the gel-like structure of phospholipid and membrane permeation may be induced by filipin even in the absence of cholesterol.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00254769
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