Cholesterol has a concentration-dependent effect on membrane organization.
It is able to control the membrane permeability by inducing conformational
ordering of the lipid chains. A systematic investigation of lipid bilayer p
ermeability is described in the present work. It takes advantage of the;tra
nsmembrane potential difference modulation induced in vesicles when an exte
rnal electric field is applied, The magnitude of this modulation is under t
he control of the membrane electrical permeability. When brought to a criti
cal value by the external field, the membrane potential difference induces
a new membrane organization. The-membrane is then permeable and prone to so
lubilized membrane protein back-insertion. This is obtained for an external
,field strength, which depends on membrane native permeability, This approa
ch was used to study the cholesterol effect on phosphatidylcholine bilayers
, Studies have been performed with lipids in gel and in fluid stales, When
cholesterol is present, it does not affect electropermeabilization and elec
troinsertion in lipids in the fluid state. When lipids are in the gel state
, cholesterol has a dose-dependent effect. When present at 6% (mol/mol), ch
olesterol prevents electropermeabilization and electroinsertion. When chole
sterol is present at more than 12%, electropermeabilization and electroinse
rtion are obtained,under milder field conditions. This is tentatively expla
ined by a cholesterol induced alteration of the hydrophobic barrier of the
bilayer core, Our results indicate that lipid membrane permeability is affe
cted by the cholesterol content.