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The antibiotic and DNA‐transfecting peptide LAH4 selectively associates with, and disorders, anionic lipids in mixed membranes
Author(s) -
Mason A. James,
Martinez Amélie,
Glaubitz Clemens,
Danos Olivier,
Kichler Antoine,
Bechinger Burkhard
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4293fje
Subject(s) - membrane , phosphatidylglycerol , chemistry , phosphatidylcholine , peptide , biochemistry , phosphatidylethanolamine , phosphatidylserine , amphiphile , liposome , phospholipid , cationic polymerization , membrane lipids , biophysics , biology , organic chemistry , copolymer , polymer
The histidine‐rich amphipathic peptide LAH4 has antibiotic and DNA delivery capabilities. The peptide has a strong affinity for anionic lipids found in the outer membrane of bacterial membranes. A role for anionic lipids in release of cationic plasmid‐containing complexes has been proposed previously, and disruption of membrane asymmetry and presentation of phosphatidylserine (PS) in the membrane outer leaflet is a general feature observed in diseased mammalian cells. Therefore, to understand the peptide‐lipid interactions in more detail, solid‐state NMR experiments on model membranes have been performed. 31 P MAS NMR on mixed phosphatidylcholine (PC)/PS and PC/phosphatidylglycerol (PG) membranes has been used to demonstrate a strong interaction between LAH4 and anionic lipids. By using deuterated lipids and wide‐line 2 H NMR when probing lipid chain order, it is demonstrated that LAH4 preferentially interacts with PS over PC and effectively disorders the anionic PS lipid fatty acyl chains. In addition, we demonstrate that the efficiency of gene transfer in vitro to different cell lines is closely related to the degree of disruption of PS acyl chains for four isomers of LAH4. This work suggests a mechanism of selective destabilization by LAH4 of anionic lipids in the membranes of cells during transfection with implications for nucleic acid delivery in vivo.