Mechanical Behavior of Axonal Actin, Spectrin, and Their Periodic Structure: A Brief Review

TL;DR

This review discusses the current understanding and limitations of the mechanical behavior of axonal actin, spectrin, and their periodic structures, highlighting gaps in quantitative data and the need for high strain rate studies relevant to brain injury.

Contribution

It provides a comprehensive summary of experimental and computational studies, identifies gaps in current knowledge, and suggests future research directions on axonal cytoskeleton mechanics.

Findings

Limited quantitative data on short vs. long actin filament mechanics.

Most spectrin studies focus on erythrocytic spectrin, not axonal spectrin.

Few studies address high strain rate responses relevant to brain injury.

Abstract

Actin and spectrin are important constituents of axonal cytoskeleton. Periodic actin and spectrin structures are found in dendrites, initial segment of axon, and main axon. Actin and spectrin periodicity has been hypothesized to be manipulating the axon stability and mechanical behavior. Several experimental and computational studies have been performed focusing on the mechanical behavior of actin, spectrin, and actin and spectrin network. However, most of the actin studies focus on typical long F actin and do not provide quantitative comparison between the mechanical behavior of short and long actin filaments. Also, most of the spectrin studies focus on erythrocytic spectrin and do not shed light on the behavior of structurally different axonal spectrin. Only a few studies have highlighted forced unfolding of axonal spectrin which are relevant to brain injury scenario. A comprehensive, strain rate dependent mechanical study is still absent in the literature. Moreover, the current opinions regarding periodic actin and spectrin network structure in axon are disputed due to conflicting results on actin ring organization as argued by recent superresolution microscopy studies. This review summarizes the ongoing limitations in this regard and provides insights on possible approaches to address them. This study will invoke further investigation into relevant high strain rate response of actin, spectrin, and actin and spectrin network shedding light into brain pathology scenario such as traumatic brain injury.