Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if electric pulses within biomedically-attainable parameters could directly influence intra-cellular components such as cytoskeletal proteins. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the bβ-tubulin's C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of new therapeutic protocols.

Department of Information Engineering Electronics and Telecommunications Sapienza University of Rome 00184 Rome Italy

Department of Physics University of Alberta Alberta T6G 1Z2 Canada

DIMEAS Politecnico di Torino 10129 Turin Italy

Institute of Photonics and Electronics of the Czech Academy of Sciences Prague 18200 Czech Republic

Medicinal Chemistry Department Heliopolis University Cairo 11777 Egypt

Rise Technology srl S Martino di Lupari Veneto 35018 Italy

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