1: Biochim. Biophys. Acta. 2007 Jul;1768(7):1830-8. Epub 2007 Apr 24. Decrease of elastic moduli of DOPC bilayers induced by a macrolide antibiotic, azithromycin. Fa N, Lins L, Courtoy PJ, DufrĂȘne Y, Van Der Smissen P, Brasseur R, Tyteca D, Mingeot-Leclercq MP. Universite catholique de Louvain, Unite de Pharmacologie Cellulaire et Moleculaire, Avenue E. Mounier 73, Bt 7370, B-1200 Brussels, Belgium. 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. Publication Types: Research Support, Non-U.S. Gov't PMID: 17537401 [PubMed - in process] Related Links Effect of the antibiotic azithromycin on thermotropic behavior of DOPC or DPPC bilayers. [Chem Phys Lipids. 2006] PMID:17007828 Interaction of the macrolide antibiotic azithromycin with lipid bilayers: effect on membrane organization, fluidity, and permeability. [Pharm Res. 2005] PMID:15835753 Real-time imaging of drug-membrane interactions by atomic force microscopy. [Biochim Biophys Acta. 2004] PMID:15328052 Elastic deformation and failure of lipid bilayer membranes containing cholesterol. [Biophys J. 1990] PMID:2249000 Effect of chain length and unsaturation on elasticity of lipid bilayers. [Biophys J. 2000] PMID:10866959