Matrix control of protein diffusion in biological membranes

Lateral diffusion coefficients of fluorescently labeled lipid and integral membrane proteins were determined in the membranes of normal and spectrin-deficient spherocytic mouse erythrocytes by the technique of fluorescence redistribution after photobleaching. The results were used to generate a mathematical description of a matrix-control model of membrane protein diffusion. In the spherocytic cells, which lack the principal components of the cytoskeletal matrix of normal cells, the diffusion coefficients of lipid (1.5 ± 0.5 x 10^-8 cm²/s) and protein (2.5 ± 0.6 x 10^-9 cm²/s) differ only by a factor of 6, close to the difference predicted on the basis of size by the two-dimensional bilayer continuum model of Saffman and Delbruck. In contrast, the membranes of normal cells show a lipid diffusion coefficient (1.4 ± 0.5 x 10^-8 cm²/s) that is some 300-fold greater than that of the membrane proteins (4.5 ± 0.8 x 10^-11 cm²/s). Analysis of these results, based on the hypothesis that protein diffusion in normal membranes is sterically hindered by a labile matrix, yields an effective matrix surface viscosity consistant with the viscoelastic mechanical properties of the membranes. Thus, a relationship is established between the deformation characteristics of the membrane and the lateral mobility of proteins suspended in the membrane.