Molecular dynamics of the cyclic lipodepsipeptides' action on model membranes: effects of syringopeptin22A, syringomycin E, and syringotoxin studied by EPR technique.
Interaction of pore-forming toxins, syringopeptin22A (SP22A), syringomycin E (SRE) and syringotoxin (ST), with model membranes were investigated. Liposomes were prepared from saturated phospholipids (DPPC or DMPC) or from binary mixtures of DPPC with varying amount of DOPC or cholesterol. The effects of the three toxins on the molecular order and dynamics of the lipids were studied using electron paramagnetic resonance (EPR) techniques. SP22A was the most-, SRE less-, and ST the least effective to increase the ordering and to decrease the rotational correlation time of the lipid molecules. The effects were more pronounced: (a) on small unilamellar vesicles (SUVs) than on multilamellar vesicles (MUVs); (b) on pure DPPC than on DPPC-cholesterol or DPPC-DOPC mixtures. Fluidity changes, determined from EPR spectra at different concentrations of the toxin, suggested the shell structure of the lipid molecules in pore formation. EPR spectra observed at different depth of the hydrocarbon chain of the lipid molecules implied an active role of the lipid molecules in the architecture of the pores created in the presence of the three toxins. Temperature dependence of the fluidity of the SUVs treated with toxins has shown an abrupt and irreversible change in the molecular dynamics of the lipid molecules at a temperature close to the pretransition, depending on the toxin species and the lipid composition. Coalescence and aggregation of the SUVs were proposed as the origin of this irreversible change.
Szabó
Zsófia
Z
Faculty of Medicine, Institute of Biophysics and Radiation Biology, Semmelweis University, VIII Puskin u 9, POB 263, Budapest H-1444, Hungary.
Budai
Marianna
M
Blaskó
Katalin
K
Gróf
Pál
P
D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol / Q000494:pharmacology; D004134:Dimyristoylphosphatidylcholine; D004578:Electron Spin Resonance Spectroscopy; D008074:Lipoproteins / Q000737:chemistry / Q000494:pharmacology*; D008081:Liposomes / Q000737:chemistry; D008560:Membrane Fluidity / Q000187:drug effects; D008566:Membranes / Q000737:chemistry / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D013696:Temperature
D008074:Lipoproteins; D008081:Liposomes; D010456:Peptides, Cyclic; D010713:Phosphatidylcholines; C402636:syringopeptin 22; C105246:syringomycin E; D015060:1,2-Dipalmitoylphosphatidylcholine; C069036:syringotoxin B; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine