Spectrin folding versus unfolding reactions and RBC membrane stiffness

Abstract

Spectrin (Sp), a key component of the erythrocyte membrane, is routinely stretched to near its fully folded contour length during cell deformations. Such dynamic loading may induce domain unfolding as suggested by recent experiments. Herein we develop a model to describe the folding/unfolding of spectrin during equilibrium or nonequilibrium extensions. In both cases, our model indicates that there exists a critical extension beyond which unfolding occurs. We further deploy this model, together with a three-dimensional model of the junctional complex in the erythrocyte membrane, to explore the effect of Sp unfolding on the membrane's mechanical properties, and on the thermal fluctuation of membrane-attached beads. At large deformations our results show a distinctive strain-induced unstiffening behavior, manifested in the slow decrease of the shear modulus, and accompanied by an increase in bead fluctuation. Bead fluctuation is also found to be influenced by mode switching, a phenomenon predicted by our three-dimensional model. The amount of stiffness reduction, however, is modest compared with that reported in experiments. A possible explanation for the discrepancy is the occurrence of spectrin head-to-head disassociation which is also included within our modeling framework and used to analyze bead motion as observed via experiment. © 2008 by the Biophysical Society.