UC Berkeley

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.