Architecture-encoded mechanics and communication in microtubules: a multiscale computational study.

Abstract

The mechanical architecture of microtubules (MTs) is crucial for modulating their functions within cells; however, the effect of varying the number of protofilaments (PFs) on the propagation of mechanical signals remains largely unexplored. Nevertheless, MTs assembled in vitro exhibit diverse PF numbers depending on the specific tubulin composition, stabilizing agents and cellular context, suggesting a regulated architectural adaptation. Here, we performed a multiscale computational study integrating molecular dynamics, dynamical network analysis and elastic network modelling to investigate the influence of the MT architecture on structural communication and mechanics. Our results highlight that an increase in PF number alters tubulin-tubulin contact patterns, reshapes lateral surface hydrophobicity and modulates the dynamics of a specific unstructured region known as the M-loop. Remarkably, we identified a correlation between the PF number, vibrational path length and bending stiffness, revealing that MTs with larger architectures propagate mechanical information less efficiently, but offer increased structural support. These findings suggest that MT architecture may serve as a design parameter influencing the propagation of mechanical signals across scales. Moreover, they may contribute to the emerging field of neuromechanobiology, where MTs are considered potential integrators of mechanical and informational processes within neurons.