Since many studies on peptide-membrane interactions are carried out on
ly with fluid phase lipid bilayers (L(alpha)-phase, absence of cholest
erol) we have investigated whether this phase is really a suitable mod
el for biological membranes. For this purpose the action of melittin o
n zwitterionic and negatively charged phospholipid bilayers, in the ab
sence and presence of 30 mol% cholesterol, was investigated by solid s
tate P-31-NMR. From the NMR point of view, it appears that systems com
posed of a single phospholipid best mimic the sterol-containing system
a few degrees below the gel-to-fluid phase transition, i.e., in the r
ippled phase (P-beta'). It is then proposed that a relatively rigid me
mbrane containing local defects, rather than a L(alpha)-bilayer, is re
quired as an appropriate model for natural membranes when probing the
action of melittin. Such requirements might bt crucial when studying p
eptide-lipid interactions.