Although the phospholipid composition of the erythrocyte membrane has been studied extensively, it remains an enigma as to how the observed composition arises and is maintained. We show here that the phospholipid composition of the human erythrocyte membrane as a whole, as well as the composition of its individual leaf lets, is closely predicted by a model proposing that phospholipid head groups tend to adopt regular, superlattice-like lateral distributions. The phospholipid composition of the erythrocyte membrane from most other mammalian species, as well as of the platelet plasma membrane, also agrees closely with the predictions of the superlattice model. Statistical analyses indicate that the agreement between the observed and predicted compositions is highly significant, thus suggesting that head group superlattices may indeed play a central role in the maintenance of the phospholipid composition of the erythrocyte membrane.

Cholesterol plays a vital role in determining the physiochemical properties of cell membranes. However, the detailed nature of cholesterol-lipid interactions is a subject of ongoing debate. Existing conceptual models, including the Condensed Complex Model, the Superlattice Model, and the Umbrella Model, identify different molecular mechanisms as the key to cholesterol-lipid interactions. In this work, the compositional dependence of the chemical potential of cholesterol in cholesterol/phosphatidylcholine mixtures was systematically measured at high resolution at 37°C by using an improved cholesterol oxidase (COD) activity assay. The chemical potential of cholesterol was found to be much higher in di18:1-PC bilayers than in di16:0-PC bilayers, indicating a more favorable interaction between cholesterol and saturated chains. More significantly, in 16:0,18:1-PC and di18:1-PC bilayers, the COD initial-reaction rate displays a series of distinct jumps near the cholesterol mole fractions ( biomembrane ͉ chemical activity ͉ free energy ͉ liposome ͉ rapid solvent exchange method C holesterol plays a vital role in determining the physiochemical properties of cell membranes. The presence of cholesterol in a lipid membrane can drastically increase lipid acyl chain order, induce cholesterol regular distributions (superlattices) or lipid raft domains, and modulate the activities of surface-acting enzymes (1-4). Despite significant technical advances in membrane research in recent years, the detailed nature of cholesterol-lipid interactions is a subject of ongoing debate. Existing conceptual models, including the Condensed Complex Model, the Superlattice Model, and the Umbrella Model, identify different molecular mechanisms as the key to cholesterol-lipid interactions in biomembranes. Clearly, there is an urgent need to establish a general cholesterol-lipid interaction theory that can explain how cholesterol supports or modulates important functions in cell membranes and perhaps can predict the behavior and functional role of cholesterol in complex membranes. Condensed Complex Model.This model was initially proposed based on a study of lipid monolayers at the air-water interface (5). The model hypothesizes the existence of low free-energy stoichiometric cholesterol-lipid complexes that occupy smaller molecular lateral areas (5, 6). At a stoichiometric composition, a sharp jump in cholesterol chemical potential ( C ) has been predicted (6, 7), as shown in Fig. 1a. Because the proposed condensed complex has a compact low-energy structure, the model explicitly predicted that cholesterol can form condensed complexes with lipids with which it can mix favorably, such as phosphatidylcholine (PC) with long saturated chains or sphingomyelins. It has also been suggested that cholesterol superlattices as well as lipid rafts are examples of the proposed condensed complexes (6,8). According to this model, the ability to form cholesterol-lipid condensed complexes represents an essential feature of cholesterol-lipid interactions.Superlatti...

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