The antimicrobial peptide gramicidin S permeabilizes phospholipid bilayer membranes without forming discrete ion channels.
We examined the permeabilization of lipid bilayers by the beta-sheet, cyclic antimicrobial decapeptide gramicidin S (GS) in phospholipid bilayers formed either by mixtures of zwitterionic diphytanoylphosphatidylcholine and anionic diphytanoylphosphatidylglycerol or by single zwitterionic unsaturated phosphatidylcholines having various hydrocarbon chain lengths, with and without cholesterol. In the zwitterionic bilayers formed by the phosphatidylcholines, without or with cholesterol, the peptide concentrations and membrane potentials required to initiate membrane permeabilization vary little as function of bilayer thickness and cholesterol content. In all the systems tested, the GS-induced transient ion conductance events exhibit a broad range of conductances, which are little affected by the bilayer composition or thickness. In the zwitterionic phosphatidylcholine bilayers, the effect of GS does not depend on the polarity of the transmembrane potential; however, in bilayers formed from mixtures of phosphatidylcholines and anionic phospholipids, the polarity of the transmembrane potential becomes important, with the GS-induced conductance events being much more frequent when the GS-containing solution is positive relative to the GS-free solution. Overall, these results suggest that GS does not form discrete, well-defined, channel-like structures in phospholipid bilayers, but rather induces a wide variety of transient, differently sized defects which serve to compromise the bilayer barrier properties for small electrolytes.
Ashrafuzzaman
Md
M
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. ashrafuz@ualberta.ca
Andersen
O S
OS
McElhaney
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RN
D000890:Anti-Infective Agents / Q000494:pharmacology*; D006096:Gramicidin / Q000494:pharmacology*; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry*
D000890:Anti-Infective Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D010743:Phospholipids; D006096:Gramicidin