Acyl chain length dependence in the stability of melittin-phosphatidylcholine complexes. A light scattering and 31P-NMR study.
Light scattering and 31P-NMR have been used to monitor the effect of the bee-toxin, melittin, on phosphatidylcholine (PC) bilayers of variable acyl chain length (from C16:0 to C20:0). Melittin interacts with all lipids provided the interaction is initiated in the lipid fluid phase. For low-to-moderate amounts of toxin (lipid-peptide molar ratios, Ri > or = 15), the system takes the form of large spheroidal vesicles, in the fluid phase, whose radius increases from 750 A with dipalmitoyl-PC (DPPC) to 1500 A with diarachinoyl-PC (DAPC). These vesicles fragment into small discoids of 100-150 A radius when the system is cooled down below Tc (the gel-to-fluid phase transition temperature). Little chain length dependence is observed for the small objects. Small structures are also detected independently of the physical state of lipids (gel or fluid) when Ri < or = 5 and provided the interaction has been made above Tc. Small discs clearly characterized for DPPC and distearoyl-PC (DSPC) lipids are much less stable with DAPC. However in the long term, all these small structures fuse into large lipid lamellae. Discs are thermodynamically unstable and kinetics of disappearance of the small lipid-toxin complexes increases as the chain length increases in the sense: DAPC >> DSPC > DPPC. Kinetics of fusion of the small discs into extended bilayers is described by a pseudo-first-order law involving a lag time after which fusion starts. Increasing the chain length decreases the lag time and increases the rate of fusion. Formation of both the large vesicles in the fluid phase and the small discs in the gel phase as well as their stability is discussed in terms of relative shapes and dynamics of both lipids and toxin.
Faucon
J F
JF
Centre de Recherche Paul Pascal, CNRS, Pessac, France.
Bonmatin
J M
JM
Dufourcq
J
J
Dufourc
E J
EJ
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D004355:Drug Stability; D007700:Kinetics; D008027:Light; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008555:Melitten / Q000737:chemistry*; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000737:chemistry*; D010758:Phosphorus; D012542:Scattering, Radiation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; C044819:1,2-diarachidonoyl-glycero-3-phosphocholine; D008555:Melitten; D015060:1,2-Dipalmitoylphosphatidylcholine; D010758:Phosphorus; C010942:1,2-distearoyllecithin