719 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
Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury.
A principal objective of spinal cord injury (SCI) research is the restoration of axonal connectivity to denervated targets. We tested the hypothesis that chemotropic mechanisms would guide regenerating spinal cord axons to appropriate brainstem targets. We subjected rats to cervical level 1 (C1) lesions and combinatorial treatments to elicit axonal bridging into and beyond lesion sites. Lentiviral vectors expressing neurotrophin-3 (NT-3) were then injected into an appropriate brainstem target, the nucleus gracilis, and an inappropriate target, the reticular formation. NT-3 expression in the correct target led to reinnervation of the nucleus gracilis in a dose-related fashion, whereas NT-3 expression in the reticular formation led to mistargeting of regenerating axons. Axons regenerating into the nucleus gracilis formed axodendritic synapses containing rounded vesicles, reflective of pre-injury synaptic architecture. Thus, we report for the first time, to the best of our knowledge, the reinnervation of brainstem targets after SCI and an essential role for chemotropic axon guidance in target selection
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
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