Electro-opening of a microtubule lattice in silico

Abstract

Modulation of the structure and function of biomaterials is essential for advancing bio-nanotechnology and biomedicine. Microtubules (MTs) are self-assembled protein polymers that are essential for fundamental cellular processes and key model compounds for the design of active bio-nanomaterials. In this in silico study, a 0.5 μs-long all-atom molecular dynamics simulation of a complete MT with approximately 1.2 million atoms in the system indicated that a nanosecond-scale intense electric field can induce the longitudinal opening of the cylindrical shell of the MT lattice, modifying the structure of the MT. This effect is field-strength- and temperature-dependent and occurs on the cathode side. A model was formulated to explain the opening on the cathode side, which resulted from an electric-field-induced imbalance between electric torque on tubulin dipoles and cohesive forces between tubulin heterodimers. Our results open new avenues for electromagnetic modulation of biological and artificial materials through action on noncovalent molecular interactions.

Keywords: Electric field; Microtubules; Molecular dynamics simulation; Proteins; Tubulin.

Graphical abstract

Fig. 1

The constitution of the simulated microtubule (MT) system. a) The size and content of the simulated unit cell, which consists of one ring of 13 tubulin heterodimers bound to guanosine triphosphate (GTP) and a water box containing ions to neutralize the charge of the system and simulate a specific (close to physiological) ionic strength. b) The system is repeated through the application of periodic boundary conditions to form arbitrarily long MTs. c) Numbering of the tubulin heterodimers in a MT ring. Black radial lines represent relative binding energies along the lateral interfaces between neighboring tubulin heterodimers in the absence of any electric field. The longer the line, the stronger the binding between the neighboring dimers. $\alpha$-tubulin is colored in blue and $\beta$-tubulin is colored in red.

Fig. 2

Snapshots of the MT ring a) when no electric field is applied, the 100 MV/m electric field is applied in the b) X, c) -X, d) Y, and e) -Y direction. Black arrows represent the dipole moment vector of each tubulin heterodimer. The four arrows on the left side depict the electric field vector orientation. The cathode and anode side of the MT ring correspond to the end and beginning of the arrow, respectively. The snapshots b)–e) are from trajectory 1 for each condition.

Fig. 3

Time evolution of the tubulin–tubulin distance a)–b) and tubulin heterodimer axial angle c)–d) and binding energy between tubulin heterodimer 2 and 3 e)–f). All data for all of the -X field direction. a), c), e) show the effect of the electric field strength for 100 MV/m and 50 MV/m, at the standard (310 K) temperature and standard ion concentration (1296 Na⁺ atoms (0.17 M) and 633 Cl⁻ atoms (0.08 M). b), d), f) show the effect of temperature at 100 MV/m and standard ion concentration. Mean values (thick line) and the standard deviation (shaded envelope) are from N = 3 trajectories. See Figs. S3, S15,S43 for data at no-field condition.

Fig. 4

Snapshots of the opening detail (all from the first trajectory of -X 100 MV/m data): a)–d) between $\alpha$-tubulin 2 and 3, e)–h) between $\beta$-tubulin 2 and 3. i)–j) Time evolution of the binding energy contribution of six highly contributing selected amino acids. Mean values (thick line) and the standard deviation (shaded envelope) are from N = 3 trajectories.

Fig. 5

The mechanism of electro-opening of the MT lattice. a) The electric field (grey arrows in the background) acts by torque (blue rounded arrows show direction of turning) on tubulin dipoles (red arrows). The magnitude of the force depends on the angle of the dipole vector with respect to the electric field vector. b) The torque on individual dipoles causes a deformation of the ring. c) The deformation accumulates at the poles of the ring. The orientation of the tubulin dipole parallel (on the right) to the electric field vector is stabilized (being at the minimum of the energy potential), whereas the orientation of the dipole anti-parallel (on the left) to the electric field is unstable (the dipole is at the peak of the energy profile). d) The opening occurs near the unstable tubulin at the interface with the lower binding energy, see Fig.1c. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).