Article (Scientific journals)
Decrease Of Elastic Moduli Of Dopc Bilayers Induced By A Macrolide Antibiotic, Azithromycin
Fa, N.; Lins, Laurence; Courtoy, Pj. et al.
2007In Biochimica et Biophysica Acta. Biomembranes, 1768 (7), p. 1830-1838
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Abstract :
[en] The elastic properties of membrane bilayers are key parameters that control its deformation and can be affected by pharmacological agents. Our previous atomic force microscopy studies revealed that the macrolide antibiotic, azithromycin, leads to erosion of DPPC domains in a fluid DOPC matrix [A. Berquand, M. P. Mingeot-Leclercq, Y. F. Dufrene, Real-time imaging of drug-membrane interactions by atomic force microscopy, Biochim. Biophys. Acta 1664 (2004) 198-205.]. Since this observation could be due to an effect on DOPC cohesion, we investigated the effect of azithromycin on elastic properties of DOPC giant unilamellar vesicles (GUVs). Microcinematographic and morphometric analyses revealed that azithromycin addition enhanced lipid membranes fluctuations, leading to eventual disruption of the largest GUVs. These effects were related to change of elastic moduli of DOPC, quantified by the micropipette aspiration technique. Azithromycin decreased both the bending modulus (k(c), from 23.1+/-3.5 to 10.6+/-4.5 k(B)T) and the apparent area compressibility modulus (K(app), from 176+/-35 to 113+/-25 mN/m). These data suggested that insertion of azithromycin into the DOPC bilayer reduced the requirement level of both the energy for thermal fluctuations and the stress to stretch the bilayer. Computer modeling of azithromycin interaction with DOPC bilayer, based on minimal energy, independently predicted that azithromycin (i) inserts at the interface of phospholipid bilayers, (ii) decreases the energy of interaction between DOPC molecules, and (iii) increases the mean surface occupied by each phospholipid molecule. We conclude that azithromycin inserts into the DOPC lipid bilayer, so as to decrease its cohesion and to facilitate the merging of DPPC into the DOPC fluid matrix, as observed by atomic force microscopy. These investigations, based on three complementary approaches, provide the first biophysical evidence for the ability of an amphiphilic antibiotic to alter lipid elastic moduli. This may be an important determinant for drug: lipid interactions and cellular pharmacology.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Fa, N.
Lins, Laurence  ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Courtoy, Pj.
Dufrene, Y.
Van Der Smissen, P.
Brasseur, Robert ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Tyteca, D.
Mingeot-Leclercq, Marie-Paule
Language :
English
Title :
Decrease Of Elastic Moduli Of Dopc Bilayers Induced By A Macrolide Antibiotic, Azithromycin
Publication date :
2007
Journal title :
Biochimica et Biophysica Acta. Biomembranes
ISSN :
0005-2736
Publisher :
Elsevier, Netherlands
Volume :
1768
Issue :
7
Pages :
1830-1838
1830-8
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 June 2010

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