Dynamics of the axon plasma membrane skeleton.

Zhaojie Chai, Shiju Gu, George Lykotrafitis

Soft matter 2023 Apr 05

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It was recently revealed via super-resolution microscopy experiments that the axon plasma membrane skeleton (APMS) comprises a series of periodically arranged azimuthal actin rings connected via longitudinal spectrin filaments forming an orthotropic network. The common perception is that APMS enhances structural stability of the axon but its impact on axon deformation is unknown. To investigate the response of the APMS to extension, we introduce a coarse-grain molecular dynamics model consisting of actin particles forming rings and chains of particles representing spectrin tetramers with repeats than can unfold. We observe that the shape of force-extension curve is initially linear and the force level depends on the extension rate. Even during the initial deformation stage, unfolding of spectrin repeats occurs, but the saw-tooth shape of the corresponding force-extension curve observed in the case of one spectrin tetramer does not appear in the case of the entire APMS. The reason is that spectrin unfolding is not synchronized across filaments during extension. If actin-spectrin associations remain intact, the force-extension response reaches a perfectly plastic region because of increased spectrin unfolding frequency. However, when actin-spectrin links dissociate, which can happen at moderate and high extension rates, APMS softens and the resistance force decreases linearly as the axon elongates until it reaches a point where the APMS is completely severed. Furthermore, when the ring-to-ring distance is maintained fixed under stretch, the resistance force relaxes exponentially as a function of time due to additional unfolding of spectrin tetramers following the Kelvin-Voigt representation of the Zener model.