Cholesterol Effect on the Dipole Potential of Lipid Membranes

Abstract

The effect of cholesterol removal by methyl-beta-cyclodextrin on the dipole potential, psi(d), of membrane vesicles composed of natural membrane lipids extracted from the kidney and brain of eight vertebrate species was investigated using the voltage-sensitive fluorescent probe di-8-ANEPPS. Cyclodextrin treatment reduced cholesterol levels by on average 80% and this was associated with an average reduction in psi(d) of 50 mV. Measurements of the effect of a range of cholesterol derivatives on the psi(d) of DMPC lipid vesicles showed that the magnitude of the effect correlated with the component of the sterol's dipole moment perpendicular to the membrane surface. The changes in psi(d) observed could not be accounted for solely by the electric field originating from the sterols' dipole moments. Additional factors must arise from sterol-induced changes in lipid packing, which changes the density of dipoles in the membrane, and changes in water penetration into the membrane, which changes the effective dielectric constant of the interfacial region. In DMPC membranes, the cholesterol-induced change in psi(d) was biphasic, i.e., a maximum in psi(d) was observed at approximately 35-45 mol %, after which psi(d) started to decrease. We suggest that this could be associated with a maximum in the strength of DMPC-cholesterol intermolecular forces at this composition.

α-Tocopherols modify the membrane dipole potential leading to modulation of ligand binding by P-glycoprotein

“…␣ -Tocopherol induced a spectral red-shift, indicative of a decrease in MDP. Also shown are the difference spectra for vesicles containing cholesterol and its oxidized derivative, 7-ketocholesterol, which have previously been demonstrated to increase and decrease the dipole potential, respectively ( 28,29 ). The concentration dependence of the change in dipole potential induced by the sterols, ␣ -tocopherol, and ␣ -tocopherol succinate in PC vesicles is shown in Fig.…”

“…These include: imparting a negative curvature stress ( 18 ) and modifying the phase behavior of lipids; decreasing the enthalpy of the gel to liquid crystalline transition by infl uencing lipid organization ( 19,20 ); and inducing phase separation as a result of preferential association with specifi c lipids ( 21,22 ). The present study investigates the effect of ␣ -tocopherol and ␣ -tocopherol succinate on the MDP, which is both a sensitive indicator of changes in lipid organization and that of surrounding water molecules ( 12,(23)(24)(25)(26)(27)(28), and directly infl uences the behavior of membrane proteins ( 25,29,30 ).…”

“…The receptor is thought to show a preference for the elevated dipole potential associated with cholesterol-rich microdomains ( 29,30 ) due to their higher lipid packing density and decreased hydration ( 28,37 ). The treatment of T-lymphocytes with methyl-␤ -cyclodextrin to disrupt these microdomains via cholesterol depletion ( 33 ) signifi cantly decreased the affi nity of saquinavir for P-gp (unpaired two-tailed t -test; P = 0.0002, R 2 = 0.98) ( Fig.…”

Energy Absorption by the Membrane Rafts in the Modulated Electro-Hyperthermia (mEHT)

“…The simulation does not consider some further complexity of the rafts like the average permittivity depends on the type of amino acids as well [21]. Based on the 91 examined proteins the average dielectric constant is in the interval 11.0 < ε protein < 25.…”

“…Simulations [20] show that the protein dielectric constant was ε protein ≅ 6 -7 in the inner protein region and ε protein ≅ 20 -30 on its wet surface. Generally, although the cholesterol and lipid contents of the raft domain cause decreasing in the relative permittivity of the inner raft area (2 < ε raft < 5), but the high density of protein chain ends lead to an outstanding raft region with high relative permittivity (40 < ε raft protein < 80), [21]. We assume the dielectric constant of the complex membrane rafts as ε raft ≈ 40.…”