Electrical behaviour and evolutionary computation in thin films of bovine brain microtubules

We report on the electrical behaviour of thin films of bovine brain microtubules (MTs). For samples in both their dried and hydrated states, the measured currents reveal a power law dependence on the applied DC voltage. We attribute this to the injection of space-charge from the metallic electrode(s). The MTs are thought to form a complex electrical network, which can be manipulated with an applied voltage. This feature has been exploited to undertake some experiments on the use of the MT mesh as a medium for computation. We show that it is possible to evolve MT films into binary classifiers following an evolution in materio approach. The accuracy of the system is, on average, similar to that of early carbon nanotube classifiers developed using the same methodology.

Electrical Oscillations of Brain Microtubules

Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities, including vesicular traffic and motility, cell division, and information transfer within neuronal processes. MTs also are highly charged polyelectrolytes. Recent in vitro electrophysiological studies indicate that different brain MT structures, including two-dimensional (2D) sheets (MT sheets) and bundles, generate highly synchronous electrical oscillations. However, no information has been heretofore available as to whether isolated MTs also engage in electrical oscillations, despite the fact that taxol-stabilized isolated MTs are capable of amplifying electrical signals. Herein we tested the effect of voltage clamping on the electrical properties of isolated non-taxol stabilized brain MTs. Electrical oscillations were observed on application of holding potentials between ±200 mV that responded accordingly with changes in amplitude and polarity. Frequency domain spectral analysis of time records from isolated MTs disclosed a richer oscillatory response as compared to that observed in voltage clamped MT sheets from the same preparation. The data indicate that isolated brain MTs are electrical oscillators that behave as “ionic-based” transistors whose activity may be synchronized in higher MT structures. The ability of MTs to generate, propagate, and amplify electrical signals may have important implications in neuronal computational capabilities.Significance StatementMicrotubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities. Recent in vitro electrophysiological studies indicate that different brain MT structures, including two-dimensional sheets and bundles, generate highly synchronous electrical oscillations. However, no information has been heretofore available as to whether isolated MTs also engage in electrical oscillations. In the present study, a broader spectrum of fundamental frequencies was always observed in isolated MTs as compared to the MT sheets. This interesting finding is consistent with the possibility that more structured MT complexes (i.e. bundles, sheets) may render more coherent response at given oscillatory frequencies and raise the hypothesis that combined MTs may tend to oscillate and entrain together. The present study provides to our knowledge the first experimental evidence for electrical oscillations of single brain MTs.

Tubulin isoform composition tunes microtubule dynamics

Microtubules polymerize and depolymerize stochastically, a behavior essential for cell division, motility, and differentiation. While many studies advanced our understanding of how microtubule-associated proteins tune microtubule dynamics in trans, we have yet to understand how tubulin genetic diversity regulates microtubule functions. The majority of in vitro dynamics studies are performed with tubulin purified from brain tissue. This preparation is not representative of tubulin found in many cell types. Here we report the 4.2-Å cryo-electron microscopy (cryo-EM) structure and in vitro dynamics parameters of α1B/βI+βIVb microtubules assembled from tubulin purified from a human embryonic kidney cell line with isoform composition characteristic of fibroblasts and many immortalized cell lines. We find that these microtubules grow faster and transition to depolymerization less frequently compared with brain microtubules. Cryo-EM reveals that the dynamic ends of α1B/βI+βIVb microtubules are less tapered and that these tubulin heterodimers display lower curvatures. Interestingly, analysis of EB1 distributions at dynamic ends suggests no differences in GTP cap sizes. Last, we show that the addition of recombinant α1A/βIII tubulin, a neuronal isotype overexpressed in many tumors, proportionally tunes the dynamics of α1B/βI+βIVb microtubules. Our study is an important step toward understanding how tubulin isoform composition tunes microtubule dynamics.