Membrane skeletal dynamics: role in modulation of red cell deformability, mobility of transmembrane proteins, and shape.

The dynamics of interactions in the membrane skeleton appear to control a variety of critical red cell membrane properties. Particularly sensitive parameters are deformability under prolonged shear and glycoprotein lateral diffusion rates. Because the dynamics of skeletal interactions can be controlled by polyanionic metabolite levels and other factors, it is suggested that metabolic abnormalities can cause skeletal dysfunction as well as abnormalities involving skeletal protein mutations. The membrane skeleton appears to be secondary to the bilayer couple in determining erythrocyte shape. Skeleton structure and dynamics do appear to influence lipid asymmetry and, by inference, the surface properties of the membrane, which will affect shape. Recent findings have shown that the erythrocyte can control its shape, and that shape control is related to hexose monophosphate shunt pathway activity. Consequently, defects in metabolism of the HMP shunt as well as structural protein abnormalities could result in abnormal cell shapes. In conclusion, the dynamics of the membrane skeleton and associated protein interactions appear to be central to many normal red cell functions and abnormal functions in disease. Much more complete knowledge of the molecular bases of these correlations, however, is required to understand fully the roles of skeletal dynamics in red cell functions.