Model of ionic currents through microtubule nanopores and the lumen

It has been suggested that microtubules and other cytoskeletal filaments may act as electrical transmission lines. An electrical circuit model of the microtubule is constructed incorporating features of its cylindrical structure with nanopores in its walls. This model is used to study how ionic conductance along the lumen is affected by flux through the nanopores when an external potential is applied across its two ends. Based on the results of Brownian dynamics simulations, the nanopores were found to have asymmetric inner and outer conductances, manifested as nonlinear IV curves. Our simulations indicate that a combination of this asymmetry and an internal voltage source arising from the motion of the C-terminal tails causes a net current to be pumped across the microtubule wall and propagate down the microtubule through the lumen. This effect is demonstrated to enhance and add directly to the longitudinal current through the lumen resulting from an external voltage source, and could be significant in amplifying low-intensity endogenous currents within the cellular environment or as a nano-bioelectronic device.Comment: 43 pages, 6 figures, revised versio

Monitoring Microtubule Mechanical Vibrations via Optomechanical Coupling

The possible disruption of a microtubule during mitosis can control the duplication of a cancer cell. Cancer detection and treatment may be possible based on the detection and control of microtubule mechanical oscillations in cells through external fields (e.g. electromagnetic or ultrasound). However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here we propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical induced transparency of an optical probe field, which can be detected with state-of the art technology. The center frequency and linewidth of the transparency peak give the resonance frequency and damping rate of the microtubule respectively, while the height of the peak reveals information about the microtubule-cavity field coupling. Our method should yield new knowledge about the physical properties of microtubules, which will enhance our capability to design physical cancer treatment protocols as alternatives to chemotherapeutic drugs

A Bio-Polymer Transistor: Electrical Amplification by Microtubules

Microtubules (MTs) are important cytoskeletal structures, engaged in a number of specific cellular activities, including vesicular traffic, cell cyto-architecture and motility, cell division, and information processing within neuronal processes. MTs have also been implicated in higher neuronal functions, including memory, and the emergence of "consciousness". How MTs handle and process electrical information, however, is heretofore unknown. Here we show new electrodynamic properties of MTs. Isolated, taxol-stabilized microtubules behave as bio-molecular transistors capable of amplifying electrical information. Electrical amplification by MTs can lead to the enhancement of dynamic information, and processivity in neurons can be conceptualized as an "ionic-based" transistor, which may impact among other known functions, neuronal computational capabilities.Comment: This is the final submitted version. The published version should be downloaded from Biophysical Journa

Self-Reduction Rate of a Microtubule

We formulate and study a quantum field theory of a microtubule, a basic element of living cells. Following the quantum theory of consciousness by Hameroff and Penrose, we let the system to reduce to one of the classical states without measurement if certain conditions are satisfied(self-reductions), and calculate the self-reduction time $\tau_N$ (the mean interval between two successive self-reductions) of a cluster consisting of more than $N$ neighboring tubulins (basic units composing a microtubule). $\tau_N$ is interpreted there as an instance of the stream of consciousness. We analyze the dependence of $\tau_N$ upon $N$ and the initial conditions, etc. For relatively large electron hopping amplitude, $\tau_N$ obeys a power law $\tau_N \sim N^b$, which can be explained by the percolation theory. For sufficiently small values of the electron hopping amplitude, $\tau_N$ obeys an exponential law, $\tau_N \sim \exp(c' N)$. By using this law, we estimate the condition for $\tau_N$ to take realistic values $\tau_N$ \raisebox{-0.5ex}{$\stackrel{>}{\sim}$} $10^{-1}$ sec as $N$ \raisebox{-0.5ex} {$\stackrel{>}{\sim}$} 1000.Comment: 7 pages, 9 figures, Extended versio

The role of structural polymorphism in driving the mechanical performance of the alzheimer's beta amyloid fibrils

Alzheimer's Disease (AD) is related with the abnormal aggregation of amyloid β-peptides Aβ1-40 and Aβ1-42, the latter having a polymorphic character which gives rise to U- or S-shaped fibrils. Elucidating the role played by the nanoscale-material architecture on the amyloid fibril stability is a crucial breakthrough to better understand the pathological nature of amyloid structures and to support the rational design of bio-inspired materials. The computational study here presented highlights the superior mechanical behavior of the S-architecture, characterized by a Young's modulus markedly higher than the U-shaped architecture. The S-architecture showed a higher mechanical resistance to the enforced deformation along the fibril axis, consequence of a better interchain hydrogen bonds' distribution. In conclusion, this study, focusing the attention on the pivotal multiscale relationship between molecular phenomena and material properties, suggests the S-shaped Aβ1-42 species as a target of election in computational screen/design/optimization of effective aggregation modulators

Structure based modeling of small molecules binding to the TLR7 by atomistic level simulations

Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In order to provide new indications for the design of Toll-Like Receptor 7 (TLR7)-targeting drugs, the mechanism of interaction between the TLR7 and two important classes of agonists (imidazoquinoline and adenine derivatives) was investigated through docking and Molecular Dynamics simulations. To perform the computational analysis, a new model for the dimeric form of the receptors was necessary and therefore created. Qualitative and quantitative differences between agonists and inactive compounds were determined. The in silico results were compared with previous experimental observations and employed to define the ligand binding mechanism of TLR7