Shear-response of the spectrin dimer-tetramer equilibrium in the red blood cell membrane.
The red cell membrane derives its elasticity and resistance to mechanical stresses from the membrane skeleton, a network composed of spectrin tetramers. These are formed by the head-to-head association of pairs of heterodimers attached at their ends to junctional complexes of several proteins. Here we examine the dynamics of the spectrin dimer-dimer association in the intact membrane. We show that univalent fragments of spectrin, containing the dimer self-association site, will bind to spectrin on the membrane and thereby disrupt the continuity of the protein network. This results in impairment of the mechanical stability of the membrane. When, moreover, the cells are subjected to a continuous low level of shear, even at room temperature, the incorporation of the fragments and the consequent destabilization of the membrane are greatly accentuated. It follows that a modest shearing force, well below that experienced by the red cell in the circulation, is sufficient to sever dimer-dimer links in the network. Our results imply 1) that the membrane accommodates the enormous distortions imposed on it during the passage of the cell through the microvasculature by means of local dissociation of spectrin tetramers to dimers, 2) that the network in situ is in a dynamic state and undergoes a "breathing" action of tetramer dissociation and re-formation.
An
Xiuli
X
Red Cell Physiology Laboratory, The New York Blood Center, New York, New York 10021, USA. xiuli_an@nybc.org
Lecomte
M Christine
MC
Chasis
Joel Anne
JA
Mohandas
Narla
N
Gratzer
Walter
W
D001665:Binding Sites; D019281:Dimerization; D004910:Erythrocyte Membrane / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry* / Q000378:metabolism; D013314:Stress, Mechanical
D010446:Peptide Fragments; D011994:Recombinant Proteins; D013049:Spectrin