52 Tubulin bond energies and microtubule biomechanics determined from nanoindentationin silico

Abstract

(2015) 52 Tubulin bond energies and microtubule biomechanics determined from nanoindentation insilico, Journal of Biomolecular Structure and Dynamics, 33:sup1,[35][36]

Mechanics of the Microtubule Seam Interface Probed by Molecular Simulations and in Vitro Severing Experiments

“…We constructed MTs comprised of 13 PFs with varied numbers of dimers per PF (8, 12, and 16) to account for any finite-size effects, as described in detail in the Section I.1 in the Supporting Information. Following our previous work, 13,16 initially we built a single ring of 13 dimers based on the atomistic structures for sets of PFs. 23 These rings were duplicated and placed longitudinally, oriented from the α to the β end until the appropriate dimer length was reached (Figure S1A).…”

“…As described above, the contact strength in the Lennard-Jones potential is set by the well-depth, h ϵ . For our regular (Reg) model, we set h ϵ to 1.9 kcal/mol for the strength of the intradimer contacts, 1.0 kcal/mol for the longitudinal contacts, and 0.9 kcal/mol for the lateral contacts, following the parametrization from our previous work, 16 which is also described in detail in ref 13. We investigated other topologies representing MT states characterized by different strengths of the various lateral and longitudinal interfaces, following our previous work.…”

“…With this goal in mind, we investigated the role of the seam in the mechanical behavior of the filament, as relevant for example during removing dimers (such as in severing). We performed simulations of the seam under compression forces using the computational framework from our previous studies of the indentation of MT lattices 13,16 mimicking atomic force microscopy (AFM) indentation experiments. 17 Our results show that the critical forces required to break the lattice at or in the vicinity of the seam are indistinguishable from the forces required to break defect-free lattices at regular B-lattice interfaces, exceeding the force that a AAA+ ATPase could exert.…”

“…18 Using a combination of indentation and retraction simulations, in conjunction with a fluctuation−dissipation theorem, 19 we determined that the strength of contacts at the seam is comparable with that for other lateral contacts in a 13 PF MT lattice. 16 These results support the idea that the seam is not a lattice defect or a mechanically weak location.…”

The α-Tubulin gene TUBA1A in Brain Development: A Key Ingredient in the Neuronal Isotype Blend

“…In contrast to longitudinal interactions, the interfaces of lateral interactions consist of flexible loop regions of α- and β-tubulin and feature prominent electrostatic contributions [ 28 , 32 ]. The binding energy of lateral interactions is predicted to be much weaker than longitudinal interactions, based on computational modeling [ 33 , 34 ]. In most cells, the lattice consists of 13 protofilaments that close into a cylindrical filament—the microtubule ( Figure 1 C).…”