A composite illustrating a view of the possible molecular basis of erythrocyte membrane mechanics in vitro and in vivo.

Read from bottom up. At “Tmod-binding site on TM5,” residues ata, d, f, and a in the N-terminal heptad repeats of TM5,1-6 functioning as the tropomodulin-binding site. At “Molecular ruler,” a complex of tropomodulin and TM5 or TM5b, in the form of homodimer or heterodimer, functioning to protect actin filaments of an uniform length.1-1,1-6 At “Actin protofilament,” a short actin protofilament of about 33-37 nm consisting of 6 G-actin per strand protected by the molecular ruler, specifying the joining of 6 spectrin tetramers. At “Hexagonal lattices of erythrocyte membrane skeleton,” geometry of the membrane skeleton defined mainly by spectrin teramers and actin protofilaments; arrows point to junctional complexes. At “Elastic deformation of erythrocyte,” elastic deformation of an erythrocyte in a flow channel,1-7 responding to a shear stress of 4.0 dyn/cm². At “Blood circulation,” “blue” erythrocytes circulating in blood vessels of a mouse yolk sac. (X-gal staining detected the expression of tropomodulin in erythrocytes reported by a “knocked in” lacZ reporter gene under the control of the endogenous Tmod promoter.) TheTmod^−/− mutation is lethal, suffering from arrests in heart development, vasculogenesis, and definitive lineage hematopoiesis.1-8 A Tmod^+/− embryo at 9.5 days of gestation is shown.