A theoretical study of dielectrophoretic effects on septins during cytokinesis under tumor treating fields

Area of Science:

• Biophysics
• Cell Biology
• Cancer Therapy

Background:

• Tumor Treating Fields (TTFields) are an FDA-approved cancer therapy.
• Septins are essential proteins regulating cytokinesis, the process of cell division.
• The precise mechanism by which TTFields affect cell division remains incompletely understood.

Purpose of the Study:

• To investigate the mechanism of TTFields' effect on tumor cell division.
• To explore the role of dielectrophoretic (DEP) forces on septin proteins during TTFields treatment.
• To evaluate different electrode configurations for maximizing TTFields' efficacy.

Main Methods:

• Utilized computational modeling to simulate TTFields' effect on septin proteins.
• Analyzed the dielectrophoretic (DEP) forces exerted by TTFields on septins.
• Compared the efficacy of a three-phase electrode configuration versus an orthogonal setup.

Main Results:

• TTFields were shown to induce negative DEP forces, displacing septins from the cleavage furrow.
• A three-phase electrode configuration demonstrated 11.2% greater effectiveness in septin displacement compared to an orthogonal setup.
• Septin mislocalization was identified as a key consequence of TTFields exposure.

Conclusions:

• TTFields interfere with cytokinesis by causing septin mislocalization, disrupting the contractile ring and midbody.
• This study provides a novel mechanism for TTFields' anti-cancer action.
• Tailoring electric field configurations to enhance negative DEP forces holds potential for improving future cancer therapies.