Electro-detachment of kinesin motor domain from microtubule in silico

Electrodynamic interaction between tumor treating fields and microtubule electrophysiological activities

“… 11 Recent studies focusing on the application of nanosecond pulsed electric fields to detach kinesin from the MT indicate that significant detachment effects are observed when the electric field intensity reaches tens of millivolt/meter. 21,38 Furthermore, even in a study where the electric field strength was lower than 100 MV/m, it did not appear to cause any discernible effect on tubulin structure, 20 among other instances documented in the literature.…”

“…Similarly, this torque is substantially smaller than the normal physiological thermal energy k B T , that is ∼4.3 × 10 −21 J. The C-terminus of β monomer carries a negative charge of approximately −19e, 21 and the tension force induced by TTFields is estimated to be about 6.1 × 10 −4 pN; however, this value is considerably less than the normal inherent electrostatic force, which typically ranges in the tens of piconewtons. Based on the above-mentioned comprehensive analysis results, we believe that TTFields are less likely to detach the kinesin form the MT through electric force and torque.…”

“…Additionally, the kinesin exhibits an overall dipole moment of approximately 1200 D, with potential fluctuations ranging from 100 to 400 D when subjected to electric fields of 100 MV/m. 21 Given that the magnitude of TTFields is significantly lower than 100 MV/m, we set the kinesin dipole moment value at 1200 D and calculated the torque using Eq. (13) to be approximately 8.0 × 10 −25 Nm.…”

“…Importantly, to generate electrostatic attraction, since the MT surface exhibits a negative potential, the motor domain of kinesin is predominantly positively charged, consistent with the electric field computation results surrounding the kinesin, 12 and the net charge of the kinesin is negative, roughly −5e. 21 To determine whether the TTFields electric force can disrupt the binding state, we examine the upper limit where the electric field is perpendicular to the MT surface. In this configuration, TTFields will generate the maximum electric force to repel kinesin from the MT surface.…”

“…In addition to the electrostatic attraction between the kinesin motor domain and the microtubule (MT) surface, the collective electric dipole moment of kinesin, along with the negatively charged C-terminus of β monomer, plays a significant role in facilitating the binding of kinesin to the MT. 21 To further investigate the influence of the electric force and torque generated by TTFields on the C-terminus of β monomer and the kinesin's dipole moment, respectively, we conducted an analysis to determine the maximum impact on the orientation of kinesin. This was achieved by configuring the direction of TTFields to be perpendicular to the dipole moment, as depicted in Fig.…”