Coarse Grain Modeling for Microtubule Mechanics

Microtubules (MTs) are cellular supramolecular structures that, in combination with actin and intermediate filaments, form the cell cytoskeleton. Within cytoskeleton filaments, MTs exhibit the highest bending stiffness. Up today, experimental techniques have not been able to investigate the origin of MTs flexural rigidity, despite the many experimental efforts done to estimate MT mechanical properties. Molecular Dynamic (MD) and Normal mode Analysis (NMA) show the potentiality for getting insight into this topic. However, these standard molecular modelling techniques are not yet able to simulate large molecular structures as MTs. In this work we developed a multiscale Coarse Grain (CG) model of an entire MT up to 180 nm long, by integrating information from MD and NMA molecular modelling. In particular, MD models were used to obtain information about the molecular conformation and arrangement of the tubulin dimers inside the MT lattice structure and Normal Mode Analysis (NMA) was used in order to study the mechanical behaviour of a MT modelled as an elastic network. MT macroscopic properties, such as bending stiffness (kf), bending modulus (Yf), stretching modulus (Ys), and persistence length (lp) were calculated on the basis of the bending and stretching modes, and results were directly compared to experimental data. Starting from the stretching modes calculated for MTs with lengths up to 180 nm, we found a non-length dependent Ys of about 0.5 GPa, which is in the range of the experimental values (Ys~0.1-2.5 GPa), and a Yb in the range of 0.13-0.35 GPa depending on MT length. These results strongly confirm the anisotropy of the MT mechanical properties.