Calculating partition coefficients of chain anchors in liquid-ordered and liquid-disordered phases

Abstract

We calculate partition coefficients of various chain anchors in liquid-ordered and liquid-disordered phases utilizing a theoretical model of a bilayer membrane containing cholesterol, dipalmitoyl phosphatidylcholine, and dioleoylphosphatidylcholine. The partition coefficients are calculated as a function of chain length, degree of saturation, and temperature. Partitioning depends on the difference between the lipid environments of the coexisting phases in which the anchors are embedded. Consequently, the partition coefficient depends on the nature of the anchor, and on the relative compositions of the coexisting phases. We find that saturated anchors prefer the denser liquid-ordered phase, and that the fraction of anchors in the liquid-ordered phase increases with increasing degree of saturation of the anchors. The partition coefficient also depends upon the location of the double bonds. Anchors with double bonds closer to the middle of the chain have a greater effect on partitioning than those near the end. Doubling the number of saturated chains increases the partitioning into the liquid-ordered phase for tails that are nearly as long or longer than those comprising the bilayer. Partitioning of such chains increases with decreasing temperature, indicating that energy considerations dominate entropic ones. In contrast, partitioning of shorter chains increases with increasing temperature, indicating that entropic considerations dominate.

Figure 1

The phase diagram of the DPPC (S), DOPC (U), and cholesterol (C), lipid bilayer at 290 K as obtained from our model. The region of the gel phase is denoted G, that of the liquid-ordered phase is denoted lo, and the liquid-disordered phase, ld. Bold lines represent the phase boundaries. Tie lines connect points at compositions in coexistence with one another. The stars represent the location where the calculations for the partition coefficient took place for T = 290 K. The region of three-phase coexistence is denoted 3. Parameters are J_ll = 3.1 × 10⁻³k_BT^∗(T^∗ = 315 K), J_lc = 0.85 J_ll, and J_cc = 0.80 J_ll.

Figure 2

Partition coefficient for various single anchor chains embedded in a membrane consisting of model DPPC, DOPC, and cholesterol. The mole fractions of the chain anchors in the liquid-order and liquid-disorder phases are x^lo and x^ld, respectively. The number of carbons in the chain is n. (A) The temperature is 290 K. The concentrations of the lo phase are x_c = 0.48, x_s = 0.30, and x_u = 0.22, whereas those of the ld phase are x_c = 0.27, x_s = 0.21, and x_u = 0.52. (B) The temperature is 300 K. The concentrations of the lo phase are x_c = 0.52, x_s = 0.26, and x_u = 0.22, whereas those of the ld phase are x_c = 0.32, x_s = 0.22, and x_u = 0.46.

Figure 3

Partition coefficient for various double-chain anchors embedded in a membrane consisting of model DPPC, DOPC, and cholesterol. The mole fractions of the chain anchors in the liquid-order and liquid-disorder phases are x^lo and x^ld, respectively. The number of carbons in the chain is n. The stars represent the values of the partition coefficient in the bulk lipid bilayer. (A) The temperature is 290 K. The concentrations of the lo phase are x_c = 0.48, x_s = 0.30, and x_u = 0.22, whereas those of the ld phase are x_c = 0.27, x_s = 0.21, and x_u = 0.52. (B) The temperature is 300 K. The concentrations of the lo phase are x_c = 0.52, x_s = 0.26, and x_u = 0.22, whereas those of the ld phase are x_c = 0.32, x_s = 0.22, and x_u = 0.46.

Figure 4

Partition coefficient for various saturated chain anchors embedded in a membrane consisting of model DPPC, DOPC, and cholesterol. The temperatures are 290 K and 300 K.