Push and Pull Forces in Lipid Raft Formation: The Push Can Be as Important as the Pull

Nearest-neighbor recognition measurements have been made using exchangeable mimics of 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine and 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine in the liquid-ordered (<i>l</i>_o) and liquid-disordered (<i>l</i>_d) states. In the <i>l</i>_d phase, the net interaction between these two lipids is repulsive. In the <i>l</i>_o phase, their interactions are neither attractive nor repulsive. These results, together with previous nearest-neighbor measurements, imply that the overall driving force for lipid domain formation in bilayers composed of high-melting lipids, low-melting lipids, and cholesterol, corresponds to a strong pull (attraction) between the high-melting lipids and cholesterol, a significant push (repulsion) between the low-melting and high-melting lipids, and a significant push between the low-melting lipids and cholesterol. In a broader context, these results provide strong support for the notion that repulsive forces play a major role in the formation of lipid rafts