Coarse-Grained Modeling and Mechanical Behaviors of Actin–Spectrin–Microtubule Complex in Axonal Cytoskeleton

Abstract

Axon is a long protrusion from the neuronal cell body whose interconnection forms the nervous network and allows biomechanical signals to be transmitted among neurons. From the mechanic’s point of view, the axon cytoskeleton consists of bundles of microtubules (MTs), cross-linked by microtubule-associated protein (MAP) tau, and supported by a periodic array of actin–spectrin rings. Yet, the fundamental question of how these actin–spectrin rings and microtubule bundles behave in synergy to provide the required mechanical strength to the whole axon is still poorly understood. Here, we developed a coarse-grained molecular dynamics model of axon to address this outstanding issue. We show that the dynamic response of spectrin filaments plays a vital role in the strain-softening of axon, which serves as a buffering mechanism for neurons to accommodate externally imposed deformation. Furthermore, the actin–spectrin structure is found to be essential for maintaining the mechanical stability of axon and allowing it to bear larger compressive forces. Our model and predictions not only explain recent experimental observations on axonal mechanics, but also provide insights on how to potentially modify the mechanical response of axonal cytoskeleton and therefore tune its capability in executing different biological duties.