Biological membranes as bilayer couples. A molecular mechanism of drug erythrocyte interactions

M. P. Sheetz, S. J. Singer

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1348 Scopus citations


It is proposed that membranes whose proteins and polar lipids are distributed asymmetrically in the two halves of the membrane bilayer can act as bilayer couples, i.e., the two halves can respond differently to a perturbation. This hypothesis is applied to the interactions of amphipathic drugs with human erythrocytes. It is proposed that anionic drugs intercalate mainly into the lipid in the exterior half of the bilayer, expand that layer relative to the cytoplasmic half, and thereby induce the cell to crenate, while permeable cationic drugs do the opposite and cause the cell to form cup shapes. This differential distribution of the drugs is attributed to interactions with the phosphatidylserine that is concentrated in the cytoplasmic half of the membrane. Impermeable amphipathic drugs intercalate only into the exterior half of the bilayer, and therefore are crenators of the intact cell. Several predictions of this hypothesis have been confirmed experimentally with erythrocytes and erythrocyte ghosts. The bilayer couple hypothesis may contribute to the explanation of many membrane mediated phenomena in cell biology. (19 references).

Original languageEnglish (US)
Pages (from-to)4457-4461
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
StatePublished - 1974
Externally publishedYes

ASJC Scopus subject areas

  • General


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