The role of the membrane skeleton in determining the shape of the huma
n red cell was probed by weakening it in situ with urea, a membrane-pe
rmeable perturbant of spectrin. Urea by itself did not alter the bicon
cave disk shape of the red cells; however, above threshold conditions
(1.5 M, 37 degrees C, 10 min), it caused an 18% reduction in the membr
ane elastic shear modulus. It also potentiated the spiculation of cell
s by lysophosphatidylcholine. These findings suggest that the contour
of the resting cell is not normally dependent on the elasticity of or
tension in the membrane skeleton. Rather, the elasticity of the skelet
on stabilizes membranes against deformation. Urea treatment also cause
d the projections induced both by micropipette aspiration and by lysop
hosphatidylcholine to become irreversible. Furthermore, urea converted
the axisymmetric conical spicules induced by lysophosphatidylcholine
into irregular, curved, and knobby spicules; i,e,, echinocytosis becam
e acanthocytosis, Unlike controls, the ghosts and membrane skeletons o
btained from urea-generated acanthocytes were imprinted with spicules.
These data suggest that perturbing interprotein associations with ure
a in situ allowed the skeleton to evolve plastically to accommodate th
e contours imposed upon it by the overlying membrane.