Thermodynamics of glycophorin in phospholipid bilayer membranes

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Abstract
We have developed a model of glycophorin in a phospholipid bilayer membrane in order to study the thermodynamics of this system and to understand the detailed behavior of recent calorimetric data. We assume that the larger glycophorin polar group can be considered as either adopting a pancakelike conformation at the bilayer interface (D state) or be directed generally away from the interface (U state) [Ruppel, D., Kapitza, H. G., Galla, H. J., Sixl, F., and Sackmann, E. (1982) Biochim. Biophys. Acta 692, 1-17]. Lipid hydrocarbon chains are described either as excited (e state) with high energy and relatively many gauche conformers or as generally extended (g state) with low energy. We performed a Monte-Carlo simulation using the Glauber and Kawasaki procedures on a triangular lattice which represents the plane of half of the bilayer. Lattice sites can be occupied either by lipid hydrocarbon chains or by model glycophorin .alpha.-helical hydrophobic cores. The states D and U are represented by hexagons of different sizes in the plane of the lattice, and the hard core repulsion between two such polar groups is accounted for by forbidding hexagon-hexagon overlap. We have studied the effect of having the glycophorin polar group interact in various ways with the lipid bilayer. We find that the protein polar group in its D state interacts, either directly or indirectly, with the lipid bilayer so as to reduce the effective lateral pressure acting on the lipid hydrocarbon chains by about 3 dyn/cm. Polar groups in their U states do not reduce this lateral pressure. We find that the region of reduced lateral pressure has a smaller area, in the plane of the bilayer, than the area of the region excluded by the protein polar group to penetration by other such polar groups, due to hard-core interactions. We find that as the protein concentration, c, increases from c = 0, the specific heat curves first broaden to a maximum at c .apprxeq. c1 while the transition enthalpy decreases approximately linearly. At this concentration, the plane of the bilayer is essentially covered with protein polar groups in their D states. As c increases further, the specific heat curves narrow while the transition enthalpy stays approximately constant. As c increases still further, the specific heat peak broadens, and the transition enthalpy decreases. Our simulations show that this behavior is understood as a consequence of the bilayer behaving like a mixture of two kinds of lipids, one with the unperturbed lateral pressure acting on the chains and the other perturbed with a reduced lateral pressure acting on the chains. We calculate a phase diagram and show that it is remarkably similar to one deduced from measurements. Finally, we make predictions about the dependence of 2H NMR line splitting upon protein concentration and propose experiments that may be performed to test prediction of the model.