The Effect of Solutes on the Temperature of Miscibility Transitions in Multicomponent Membranes

Abstract

We address questions posed by experiments that show small-chain alcohols reduce the miscibility transition temperature when added to giant plasma membrane vesicles (GPMVs), but increase that temperature when added to giant unilamellar vesicles. In giant unilamellar vesicles the change in temperature displays a definite minimum, between decanol and tetradecanol, as a function of alcohol chain length; in GPMVs there is no such minimum. To emphasize the competition between internal entropies of the components and the interactions between them, we model the system as consisting of three different linear polymers. Two of them are the constituents of a liquid, one that can undergo a miscibility transition. To this liquid is added the third polymer component, which represents the short-chain alcohol. We show that, within Flory-Huggins theory, the addition of alcohol causes an increase or decrease of the miscibility transition temperature depending upon the competition of two effects. The first is the dilution of the interactions between the two components of the liquid caused by the introduction of the alcohol. This tends to lower the transition temperature. The second effect is the preferential partitioning of the alcohol into one phase of the liquid or the other. This tends to raise the transition temperature irrespective of which phase the alcohol prefers. This second effect is the smallest, and the decrease in transition temperature the largest, when the alcohol partitions equally between the two phases. Such equal partitioning occurs when the effect of the entropic excluded volume interactions (which cause the alcohol to prefer one phase) just balances the effect of the direct interactions, which cause it to prefer the other. These results allow us to make several predictions, and to propose an explanation for the different behavior of the transition temperature in GPMVs and giant unilamellar vesicles that results from the addition of alcohols.

Figure 1

Change in transition temperature upon the addition of n-alcohol to GPMVs. Concentrations of solute are all equal to a fiducial given in Pringle et al. (23). Figure is from Cornell et al. (4).

Figure 2

Change in transition temperature upon the addition of n-alcohol to a GUV composed of mol fractions 35:35:30 DOPC/DPPC/cholesterol. Concentrations of solute are all three times a fiducial given in Pringle et al. (23). Figure is from Cornell et al. (4).

Figure 3

Schematic phase diagram in the space of temperature, T, and compositions of the solvent component A and solute S. (a) Given here is an illustration of the case in which addition of solute raises the miscibility transition temperature. One is looking in the direction of increasing solute concentration. The line of critical points is shown with short dashes. The nearest plane to the viewer is the plane of zero solute fraction. The longer dashed lines indicate a plane at some nonzero solute concentration. (b) The case in which addition of solute lowers the transition temperature is shown. One is looking in the direction of decreasing solute concentration. The vertical plane is that of zero solute concentration.

Figure 4

Ratio of the mol fractions in the lo phase to ld phase, X^lo/X^ld, for several kinds of single chains of length n in a system of DOPC/DPPC/cholesterol. C_n:0 denotes a chain of length n and no double bonds, whereas C_n:1c9 denotes a chain of length n with one double bond at the ninth position from the head of the chain, etc. The temperature is 290 K. Illustration is from Uline et al. (10). To see this figure in color, go online.