Lateral diffusion coefficients of fluorescently labeled lipids 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 Delbrück [Saffman, P. G. l& Delbrück, M. (1975) Proc. Natl. Acad. Sci. USA 72, 3111-3113]. 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 consistent 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.
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