Membrane proteins of intact human erythrocytes were labeled with two fluorescent sulfhydryl reagents. The tagged cells were then subjected to simultaneous liposome treatments for either depletion or enrichment of membrane cholesterol content. Cholesterol depletion, which reduces membrane microviscosity, was followed by a series of fluorescence changes all indicating masking of the membrane proteins. Conversely increasing the membrane microviscosity by cholesterol enrichment resulted in an appreciable increase of the protein exposure to the aqueous surrounding. These findings strongly suggest that membrane proteins may be vertically displaced upon changes in lipid fluidity, a mechanism that may play a significant role in modulation of antigens and receptors in vivo.
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