We applied the Blundell-Terentjev theory of semi-flexible polymers to predict the mechanics of spectrin tetramer as a stiff polymer in the red blood cells. Previous experimental imaging data showed that the spectrin tetramer was a straight polymer rather than a random coil due to each linker region consisting of a continuous alpha helix. Topological models, such as the Chinese finger trap model, were proposed. However, the development of a mechanical model for spectrin based on these topological propositions as a stiff polymer was not achieved. This has led to previous theoretical treatments of spectrin as flexible polymer chain models, such as a freely jointed chain and a flexible worm-like chain, even though recent observations of spectrin suggest that it would be more phenomenologically accurate to treat spectrin as a stiff polymer. By predicting the local persistence lengths using all-atom molecular dynamics simulations of a full-length spectrin tetramer, we found that its persistence length was indeed larger than its contour length. After fitting the parameters of semi-flexible models based on simulations, we found that this new model could predict the mechanics of the spectrin network in red blood cells more accurately than previous flexible polymer models. We constructed the constitutive model of the spectrin network based on the predicted force-extension curve and spectrin length/orientation distributions obtained from experimental imaging. Based on this microstructure-based constitutive model, we used the finite element method and the boundary element method to predict the biconcave shape, tank-treading motion, and micropipette aspiration of a red blood cell with the spectrin network. Our model showed that the new model of spectrin and its network fitted various experimental data much better with the same set of parameters than the existing models. These results might completely change the picture of the traditional spectrin mechanics.
Peng et al. (2026) studied this question.