Behavior of the DPH fluorescence probe in membranes perturbed by drugs
| Autor: | Mariusz Kepczynski, Piotr Jurkiewicz, Chetan Poojari, Tomasz Róg, Rumiana Dimova, Rafael de Lira, Rafał Petka, Natalia Wilkosz |
|---|---|
| Přispěvatelé: | Tampere University, Physics, Research group: Biological Physics and Soft Matter, Research area: Computational Physics, Department of Physics |
| Rok vydání: | 2019 |
| Předmět: |
DYNAMICS
PARTICLE MESH EWALD Antifungal Agents 1 6-diphenyl-1 3 5-hexatriene Lipid bilayers Surface Properties 116 Chemical sciences 030303 biophysics Antifungal drug Fluorescence Polarization Molecular Dynamics Simulation MODEL MEMBRANES 114 Physical sciences Biochemistry 03 medical and health sciences BIOPHYSICAL PROPERTIES Membrane fluidity AA FORCE-FIELD Anisotropy Lipid bilayer Molecular Biology Fluorescent Dyes STAPHYLOCOCCUS-AUREUS 030304 developmental biology 0303 health sciences Molecular dynamics simulations Chemistry LIPID-MEMBRANES CHOLESTEROL Bilayer Organic Chemistry technology industry and agriculture Fluorescence recovery after photobleaching Cell Biology UNILAMELLAR VESICLES Membrane Phosphatidylcholines Biophysics lipids (amino acids peptides and proteins) DPPC Itraconazole Diphenylhexatriene Hydrophobic and Hydrophilic Interactions Fluorescence anisotropy |
| Zdroj: | Chemistry and Physics of Lipids |
| ISSN: | 0009-3084 |
| Popis: | 1,6-Diphenyl-1,3,5-hexatriene (DPH) is one of the most commonly used fluorescent probes to study dynamical and structural properties of lipid bilayers and cellular membranes via measuring steady-state or time-resolved fluorescence anisotropy. In this study, we present a limitation in the use of DPH to predict the order of lipid acyl chains when the lipid bilayer is doped with itraconazole (ITZ), an antifungal drug. Our steady-state fluorescence anisotropy measurements showed a significant decrease in fluorescence anisotropy of DPH embedded in the ITZ-containing membrane, suggesting a substantial increase in membrane fluidity, which indirectly indicates a decrease in the order of the hydrocarbon chains. This result or its interpretation is in disagreement with the fluorescence recovery after photobleaching measurements and molecular dynamics (MD) simulation data. The results of these experiments and calculations indicate an increase in the hydrocarbon chain order. The MD simulations of the bilayer containing both ITZ and DPH provide explanations for these observations. Apparently, in the presence of the drug, the DPH molecules are pushed deeper into the hydrophobic membrane core below the lipid double bonds, and the probe predominately adopts the orientation of the ITZ molecules that is parallel to the membrane surface, instead of orienting parallel to the lipid acyl chains. For this reason, DPH anisotropy provides information related to the less ordered central region of the membrane rather than reporting the properties of the upper segments of the lipid acyl chains. publishedVersion |
| Databáze: | OpenAIRE |
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