Reference : Decrease Of Elastic Moduli Of Dopc Bilayers Induced By A Macrolide Antibiotic, Azithr...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Decrease Of Elastic Moduli Of Dopc Bilayers Induced By A Macrolide Antibiotic, Azithromycin
Fa, N. [> > > >]
Lins, Laurence mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Courtoy, Pj. [> > > >]
Dufrene, Y. [> > > >]
Van Der Smissen, P. [> > > >]
Brasseur, Robert mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Tyteca, D. [> > > >]
Mingeot-Leclercq, Mp. [> > > >]
Biochimica et Biophysica Acta-Biomembranes
Yes (verified by ORBi)
[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.
Researchers ; Professionals

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