Models of human erythrocyte membrane showing major populations of band 3 and their likely models of lateral diffusion. (A) Lateral view of erythrocyte membrane showing major membrane-spanning proteins including: glycophorin C (GPC), Rh protein (Rh), band 3 (3), the glucose transporter (GLUT 1), Rh-associated glycoprotein (RhAG), CD47, and glycophorin A (GPA). Labeled peripheral membrane proteins include: spectrin, ankyrin, protein 4.1 (4.1) and protein 4.2 (4.2), adducin, P55, and dematin. Note that the 3 hypothesized populations of band 3 include freely diffusing band 3, band 3 in an ankyrin complex, and band 3 in the junctional complex. (B) Top view of hexagonal spectrin network showing expected mobilities of band 3. Three types of band 3 interactions are hypothesized, each with its predicted mobility: (1) free band 3 should exhibit high mobility over short time scales, but lower mobility with periodically confined diffusion (hop diffusion) over longer time scales, (2) band 3 bound to the spectrin-actin junctional complex through adducin should also show a limited (possibly even more limited than case 3) diffusion over short time periods and similarly restricted long time diffusion and (3) band 3 linked to spectrin tetramers through ankyrin should display limited mobility over short time periods and significantly restricted motion over long time periods.