Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton

Although much evidence suggests that the plasma membrane of eukaryotic cells is not homogenous, the precise architecture of this important structure has not been clear. Here we use transmission electron microscopy of plasma membrane sheets and specific probes to show that most or all plasma membrane-associated proteins are clustered in cholesterol-enriched domains (islands) that are separated by protein-free and cholesterol-low membrane. These islands are further divided into subregions, as shown by the localization of raft and non-raft markers to specific areas. Abundant actin staining and inhibitor studies show that these structures are connected to the cytoskeleton and at least partially depend on it for their formation and/or maintenance.