1: Biochim Biophys Acta. 2004 Aug 30;1664(2):198-205. 

Real-time imaging of drug-membrane interactions by atomic force microscopy.

Berquand A, Mingeot-Leclercq MP, Dufrene YF.

Unite de chimie des interfaces, Universite catholique de Louvain, Croix du Sud
2/18, B-1348 Louvain-la-Neuve, Belgium.

Understanding drug-biomembrane interactions at high resolution is a key issue in
current biophysical and pharmaceutical research. Here we used real-time atomic
force microscopy (AFM) imaging to visualize the interaction of the antibiotic
azithromycin with lipid domains in model biomembranes. Various supported lipid
bilayers were prepared by fusion of unilamellar vesicles on mica and imaged in
buffer solution. Phase-separation was observed in the form of domains made of
dipalmitoylphosphatidylcholine (DPPC), sphingomyelin (SM), or SM/cholesterol
(SM/Chl) surrounded by a fluid matrix of dioleoylphosphatidylcholine (DOPC).
Time-lapse images collected following addition of 1 mM azithromycin revealed
progressive erosion and disappearance of DPPC gel domains within 60 min. We
attribute this effect to the disruption of the tight molecular packing of the
DPPC molecules by the drug, in agreement with earlier biophysical experiments.
By contrast, SM and SM-Chl domains were not modified by azithromycin. We suggest
that the higher membrane stability of SM-containing domains results from
stronger intermolecular interactions between SM molecules. This work provides
direct evidence that the perturbation of lipid domains by azithromycin strongly
depends on the lipid nature and opens the door for developing new applications
in membrane biophysics and pharmacology.

PMID: 15328052 [PubMed - indexed for MEDLINE]