Buckling Behavior of Individual and Bundled Microtubules

Abstract

As the major structural constituent of the cytoskeleton, microtubules (MTs) serve a variety of biological functions that range from facilitating organelle transport to maintaining the mechanical integrity of the cell. Neuronal MTs exhibit a distinct configuration, hexagonally packed bundles of MT filaments, interconnected by MT-associated protein (MAP) tau. Building on our previous work on mechanical response of axonal MT bundles under uniaxial tension, this study is focused on exploring the compression scenarios. Intracellular MTs carry a large fraction of the compressive loads sensed by the cell and therefore, like any other column-like structure, are prone to substantial bending and buckling. Various biological activities, e.g., actomyosin contractility and many pathological conditions are driven or followed by bending, looping, and buckling of MT filaments. The coarse-grained model previously developed in our lab has been used to study the mechanical behavior of individual and bundled in vivo MT filaments under uniaxial compression. Both configurations show tip-localized, decaying, and short-wavelength buckling. This behavior highlights the role of the surrounding cytoplasm and MAP tau on MT buckling behavior, which allows MT filaments to bear much larger compressive forces. It is observed that MAP tau interconnections improve this effect by a factor of two. The enhanced ability of MT bundles to damp buckling waves relative to individual MT filaments, may be interpreted as a self-defense mechanism because it helps axonal MTs to endure harsher environments while maintaining their function. The results indicate that MT filaments in a bundle do not buckle simultaneously implying that the applied stress is not equally shared among the MT filaments, that is a consequence of the nonuniform distribution of MAP tau proteins along the bundle length. Furthermore, from a pathological perspective, it is observed that axonal MT bundles are more vulnerable to failure in compression than tension.

Torsional Behavior of Axonal Microtubule Bundles

“…Obviously, a mere computational model, without validation by experimental or other computational studies, could not provide comprehensive and accurate results on this subject. However, the accuracy of our MT bundle model was previously assessed in two studies on tension and compression of individual and bundled MTs (32,33), where a large body of experimental results were used for validation. Based on the reported critical number of turns of 1.7 for single MTs subjected to torsion (35), which gives us a rough approximation of the expected range of critical number of turns, we chose to explore a wider range of up to seven bundle turns.…”

“…Our previously developed model has proven useful in studying the mechanical behavior of MTs under external tensile and compressive forces (32,33). We further developed this model to explore the behavior of MTs under torsional stress (Fig.…”

“…We study mechanical behavior of MT bundles, their relaxation behavior, and the influence of crosslink spacing under pure torsion. Moreover, the combination of tension and torsion is examined with particular attention paid to the influence of torsion on bundle failure, in contrast to our previous studies (32,33). The bundle energy distribution is monitored in all different case studies.…”

“…We have previously investigated the mechanical response of MT bundles under tension and compression (32,33). Our former study on tension of MTs showed that the failure of MT bundles occurs primarily due to the failure of MAP tau proteins.…”

Multiscale Modelling of Blast-Induced TBI Mechanobiology - From Body to Neuron to Molecule

“…These responses may provide partial explanation of recently reported 'white matter plasticity' in mTBI [61][62][63] . Mathematical models of the mechanical deformation and damage to intraaxonal MTs and associated protein Tau have been recently reported [24][25]30,38,[64][65] . First even FEM based 3D micro-injury model of a large network of MTs (elastic beams) linked by Tau dimers (viscoelastic bar elements) is presented.…”