Tubulin's response to external electric fields by molecular dynamics simulations

Abstract

Tubulin heterodimers are the building blocks of microtubules and disruption of their dynamics is exploited in the treatment of cancer. Electric fields at certain frequencies and magnitudes are believed to do the same. Here, the tubulin dimer’s response to external electric fields was determined by atomistic simulation. External fields from 50 to 750 kV/cm, applied for 10 ns, caused significant conformational rearrangements that were dependent upon the field’s directionality. Charged and flexible regions, including the α:H1-B2 loop, β:M-loop, and C-termini, were susceptible. Closer inspection of the α:H1-B2 loop in lower strength fields revealed that these effects were consistent and proportional to field strength, and the findings indicate that external electric fields modulate the stability of microtubules through conformational changes to key loops involved in lateral contacts. We also find evidence that tubulin’s curvature and elongation are affected, and external electric fields may bias tubulin towards depolymerization.

Reversible and Irreversible Modulation of Tubulin Self‐Assembly by Intense Nanosecond Pulsed Electric Fields

“…A perspective modulation strategy to overcome the above‐mentioned limitations is looming from the extraordinary electrical properties of tubulin dimers, and suggests efficient targeting of tubulin with electromagnetic fields . Recent studies showed that intense nanosecond pulsed electric field affected cellular fibrous structures such as actin filaments and MTs .…”

Intense Pulsed Electric Fields Denature Urease Protein

“…Voltage pulses with a duration of 5 ns, as shown in Figure 1, measured in a 1 mm gap cuvette using a capacitive divider, were delivered to the cuvette for 500 times at a repetition frequency of 3 Hz. 20 The maximum electric field 34 URABE ET AL. strength in the cuvette was 300 kV/cm, and the repetitive pulsing had a slight thermal effect, with a temperature rise of 3°C (Fig.…”

“…So far, numerous articles have proposed several effects of electric fields to proteins: conformational effects and chemical effects. 21,[32][33][34] The main cause of the tertiary and quaternary structures deformation of urease might be one of those effects. However, it is necessary to collect enormous data to determine the main factor.…”

2 MV/cm Pulsed Electric Fields Promote Transthyretin Amyloid Disintegration

“…Because it is technically difficult to apply strong electric fields to liquid samples, most previous studies have used numerical calculations. 17–19 According to such calculations, proteins change their three-dimensional structures under a static electric field of 1 MV/cm. Therefore, we focused on amyloid destruction theory, which speculates that amyloid is destroyed under fields stronger than 1 MV/cm which last longer than 400 ns.…”