Most cited article - PubMed ID 22575306
Mechano-electrical vibrations of microtubules--link to subcellular morphology
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.
- MeSH
- Electric Stimulation * methods MeSH
- Humans MeSH
- Molecular Dynamics Simulation * MeSH
- Static Electricity MeSH
- Tubulin physiology MeSH
- Binding Sites MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Tubulin MeSH
The knowledge of mechanisms underlying interactions between biological systems, be they biomacromolecules or living cells, is crucial for understanding physiology, as well as for possible prevention, diagnostics and therapy of pathological states. Apart from known chemical and direct contact electrical signaling pathways, electromagnetic phenomena were proposed by some authors to mediate non-chemical interactions on both intracellular and intercellular levels. Here, we discuss perspectives in the research of nanoscale electromagnetic interactions between biosystems on radiofrequency and microwave wavelengths. Based on our analysis, the main perspectives are in (i) the micro and nanoscale characterization of both passive and active radiofrequency properties of biomacromolecules and cells, (ii) experimental determination of viscous damping of biomacromolecule structural vibrations and (iii) detailed analysis of energetic circumstances of electromagnetic interactions between oscillating polar biomacromolecules. Current cutting-edge nanotechnology and computational techniques start to enable such studies so we can expect new interesting insights into electromagnetic aspects of molecular biophysics of cell signaling.
- Keywords
- Bioelectrodynamics, Biomolecules, Cell signaling, Electromagnetic field, Microwaves, Radiofrequency,
- MeSH
- Macromolecular Substances metabolism MeSH
- Microwaves * MeSH
- Radiobiology methods MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Macromolecular Substances MeSH
The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells--a strategy used in novel methods for cancer treatment.
