Electric field effect on cholesterol–phospholipid complexes

Abstract

Monolayer mixtures of dihydrocholesterol and phospholipids at the air-water interface are used to model membranes containing cholesterol and phospholipids. Specific, stoichiometric interactions between cholesterol and some but not all phospholipids have been proposed to lead to the formation of condensed complexes. It is reported here that an externally applied electric field of the appropriate sign can destabilize these complexes, resulting in their dissociation. This is demonstrated through the application of an electric field gradient that leads to phase separations in otherwise homogeneous monolayers. This is observed only when the monolayer composition is close to the stoichiometry of the complex. The electric field effect is analyzed with the same mean field thermodynamic model as that used previously to account for pairs of upper miscibility critical points in these mixtures. The concentrations of dihydrocholesterol, phospholipid, and complex vary strongly and sometimes discontinuously in the monolayer membrane in the field gradient. The model is an approximation to a two-dimensional liquid in which molecules freely exchange between free and complexed form so that the chemical potentials are constant throughout the membrane. The calculations are illustrated for a complex of about 15 molecules, composed of 5 cholesterol molecules and 10 phospholipid molecules.monolayers ͉ membranes ͉ chemical activity ͉ phase separations ͉ sphingomyelin

A Thermodynamic Model for Extended Complexes of Cholesterol and Phospholipid

“…6, the average size of the complexes in the mixture, ͗n͘, is Ͼ10 4 at the stoichiometric composition, but decreases by more than an order of magnitude within a few mole percent of this composition. This effect is reminiscent of electric-field experiments conducted with cholesterol/ phospholipid monolayers, in which the response to the electric field was found to be restricted to a narrow range around the stoichiometric composition (Radhakrishnan and McConnell, 2000b). A complex having 1:3 stoichiometry and n ϭ 10 4 would have a length of ϳ30 m in the case of a linear complex, or a diameter of ϳ0.2 m in the case of a round two-dimensional complex.…”

Structural changes in single membranes in response to an applied transmembrane electric potential revealed by time-resolved neutron/X-ray interferometry

“…Although a simple calculation might suggest that the energy of interaction of this dipole with the applied electric field should be much smaller than kT, a small domain of dipoles within the 2-D liquid phase of the POPC monolayer could increase the magnitude of the interaction [7]. For the POPC monolayer to thin locally would require the existence of such domains of sufficient size so as to avoid the energy penalty of hydrophobic mismatch [8].…”

Depolarization affects the lateral microdomain structure of yeast plasma membrane

“…The transmembrane electric field not only facilitates translocation of ions and nutrients across the plasma membrane, but also directly affects the membrane structure. In artificial lipid bilayers, the effects of the membrane potential on membrane organization and its physical properties include experimentally documented shifts in phase‐transition temperature , destabilization of cholesterol–phospholipid complexes and theoretically proposed domain separation of lipids with different acyl chain lengths . In the latter study, the proposal was generalized to biomembranes: ‘in a biological system close to spontaneous de‐mixing, the cell membrane could be switched from a one‐phase state to a two‐phase state by increasing the membrane potential … and vice versa' .…”