583 research outputs found
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 (the
mean interval between two successive self-reductions) of a cluster consisting
of more than neighboring tubulins (basic units composing a microtubule).
is interpreted there as an instance of the stream of consciousness. We
analyze the dependence of upon and the initial conditions, etc.
For relatively large electron hopping amplitude, obeys a power law
, which can be explained by the percolation theory. For
sufficiently small values of the electron hopping amplitude, obeys an
exponential law, . By using this law, we estimate the
condition for to take realistic values
\raisebox{-0.5ex}{} sec as \raisebox{-0.5ex}
{} 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
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