Permeability properties of phospholipid membranes: effect of cholesterol and temperature.

Abstract

1. 1. The effect of cholesterol on the permeability and electrical properties of phospholipid membranes has been studied with unilamellar vesicles and with bilayers (black films). The presence of cholesterol produces a decrease in the permeability coefficients of phospholipid vesicles to Na+, K+, Cl- and glucose; it also results in an increase in the electrical resistance and capacitance of phospholipid bilayers. The effect is apparent with negative, neutral as well as with positively charged membranes. 2. 2. Temperature studies indicate that cholesterol has a considerable effect on the Arrhenius activation energies (Ea), for the diffusion of all the solutes studied. However the effect on the Ea for cation diffusion is a large decrease (from 27–30 kcal/mole to 13–14 kcal/mole) while the effect on the Ea, for Cl- and glucose is only a slight increase (from 14 to 17 kcal/mole and from 19 to 22 kcal/mole, respectively). Values of free energies for activation (ΔF+) are also evaluated and are in the range of 20–24 kcal/mole for all solutes studied, ΔF+ being increased only by about 0.5 kcal/mole upon the introduction of cholesterol. 3. 3. An analysis of the Arrhenius plots allowing for the energies of activation to be temperature dependent (a slight decrease with increasing temperature) indicates that linearization of the plot would result in erroneously large activation energies. Temperature-dependent structural changes have been observed by X-ray diffraction as thinning of the membrane with increasing temperature, and would probably be inhibited by the presence of cholesterol. This argument is offered as an explanation for the cholesterol effect on cation activation energies. Possible mechanisms for the cholesterol effect on the permeation of charged and uncharged species are outlined.