Browsing by Author "Bhuiyan, Asadullah"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Investigation of the electrical properties of microtubule ensembles under cell-like conditions(2020) Aarat, Kalra P.; Patel, Sahil D.; Bhuiyan, Asadullah; Preto, Jordane; Scheuer, Kyle G.; Mohammed, Usman; Lewis, John D.; Rezania, Vahid; Shankar, Karthik; Tuszynski, Jack A.Microtubules (MTs) are cylindrical polymers composed of the heterodimers of protein α, β- tubulin that play a variety of well-recognised intracellular roles, such as maintaining the shape and rigidity of the cell, aiding in positioning and stabilisation of the mitotic spindle for allowing chromosomal segregation, acting as ‘rails’ for macromolecular transport and forming cilia and flagella for cell movement. Since the tubulin dimer possesses a high negative electric charge of ~23e and a large intrinsic high dipole moment of approximately 1750 D [1,2], MTs have been implicated in electrically-mediated biological roles [3,4,5,6]. They have been modelled as nanowires capable of enhancing ionic transport [7,8], and simulated to receive and attenuate electrical oscillations [4,9,10,11]. In solution, MTs have been shown to align with applied electric fields [2,12,13,14,15,16]. Recently, MTs have also been modelled as the primary cellular targets for low-intensity (1–2 V), intermediate-frequency (100–300 kHz) electric fields termed TTFields (tumour-treating electric fields) that inhibit cancer cell proliferation, in particular glioma [17,18,19]. Indeed, MTs have been reported to decrease buffer solution resistance [12,13], leading to a conductance peak at frequencies close to the TTField regime [20]. While these studies show that MTs are highly sensitive to external electric fields, answers to the questions ‘How do MTs effect a solution’s capacitance?’ and ‘What is the capacitance of a single MT?’ are still elusive and crucial to the determination of the dielectric properties of living cells. The tubulin concentration in mammalian cells varies in the micromolar range (~10–25 μM) [21,22]. In vitro, polymerizing tubulin at such high concentrations can lead to the formation of entangled networks, confounding quantification of the individual MT response to electric fields. Electro-rotation, di-electrophoresis and impedance spectroscopy are thus performed using low concentrations of tubulin, in the nanomolar regime, to enable robust observation of individual MTs.Item Tubulin and microtubules as molecular targets for ttfield therapy(2019) Kalra, Aarat P.; Patel, Sahil D.; Bhuiyan, Asadullah; Rezania, Vahid; Lewis, John; Shankar, Karthik; Tuszynski, Jack A.TTField (Tumor-treating field) therapy utilizes low intensity intermediate frequency AC electric fields to reduce the spread of cancer. While it has attained FDA approval for the treatment of recurrent glioblastoma multiforme, the exact molecular targets of TTField therapy are not well understood. Microtubules are pipe-like polymers of the highly charged (–31 e) and strongly dipolar (dipole moment 1666 D) protein, α, β- tubulin. Studies on the electrical properties of microtubules have recently gained interest, with them being modelled as molecular targets of TTFields. Here, we experimentally show that while tubulin polymerized into microtubules leads to an increase in solution capacitance, unpolymerized tubulin has no appreciable effect. To the best of our knowledge, we present the first experimental quantification of the capacitance of a 20 μm-long microtubule. Using these results, we calculate the resonant frequency of a microtubule meshwork in a cell-like environment to be in the TTField regime. Our results utilize high ionic strength solutions and cell-like concentrations of tubulin to show the potential of microtubules as the targets of TTField action and as intracellular charge-storage devices. We conclude with a hypothesis of an electrically-tunable cell, where the dielectric properties of the cytoskeleton alter local and global charge storage and transport.