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.

Tubulin response to intense nanosecond-scale electric field in molecular dynamics simulation / Marracino, P.; Havelka, D.; Prusa, J.; Liberti, M.; Tuszynski, J.; Ayoub, A. T.; Apollonio, F.; Cifra, M.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 9:1(2019), pp. 1-14. [10.1038/s41598-019-46636-4]

Tubulin response to intense nanosecond-scale electric field in molecular dynamics simulation

Marracino P.
Primo
Membro del Collaboration Group
;
Liberti M.
Membro del Collaboration Group
;
Apollonio F.
Penultimo
Membro del Collaboration Group
;
2019

Abstract

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.
2019
molecular dynamics; protein; tubulin; intense electric fields
01 Pubblicazione su rivista::01a Articolo in rivista
Tubulin response to intense nanosecond-scale electric field in molecular dynamics simulation / Marracino, P.; Havelka, D.; Prusa, J.; Liberti, M.; Tuszynski, J.; Ayoub, A. T.; Apollonio, F.; Cifra, M.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 9:1(2019), pp. 1-14. [10.1038/s41598-019-46636-4]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1412004
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