Mitotic spindle and polar cellular components

The mitotic machinery and charged cellular components represent the structural framework and polar molecules, such as tubulin and septins, required for eukaryotic cell division. These components are characterized by significant electric dipole moments, which allow them to be manipulated by external electric fields during the highly organized process of mitosis (Kirson et al., 2007, PNAS). In oncological applications, this target is exploited by Tumor Treating Fields (TTFields), which deliver low-intensity, intermediate-frequency alternating electric fields to disrupt the assembly of the mitotic spindle and the localization of the contractile ring. This disruption leads to mitotic arrest, abnormal chromosome segregation, and subsequent cell death through apoptosis or permanent cell cycle arrest (Gera et al., 2015, PLoS One). Beyond physical modalities, this machinery is also the target of various antimitotic drugs, including taxanes and vinca alkaloids, which bind to tubulin to alter microtubule dynamics. Targeting these components is a proven strategy for treating aggressive malignancies like glioblastoma multiforme and malignant pleural mesothelioma (Rominiyi et al., 2021, British Journal of Cancer).

Other names

Mitotic machinery and charged cellular components during cell divisionMitotic machineryPolar cellular componentsTubulin and septin dimersMitotic spindle apparatus

The primary mechanism involves the application of intermediate-frequency (100–500 kHz) alternating electric fields that exert dielectrophoretic forces on highly polar mitotic proteins, specifically tubulin and septins. This leads to two main inhibitory effects: (1) interference with the alignment of tubulin dimers, which prevents proper mitotic spindle assembly, and (2) dielectrophoresis of polar molecules toward the high-field intensity region at the cleavage furrow, which disrupts cytokinesis and leads to mitotic catastrophe (Kirson et al., 2007; Gera et al., 2015).