24 research outputs found
Simulated Cytoskeletal Collapse via Tau Degradation
We present a coarse-grained two dimensional mechanical model for the
microtubule-tau bundles in neuronal axons in which we remove taus, as can
happen in various neurodegenerative conditions such as Alzheimer's disease,
tauopathies, and chronic traumatic encephalopathy. Our simplified model
includes (i) taus modeled as entropic springs between microtubules, (ii)
removal of taus from the bundles due to phosphorylation, and (iii) a possible
depletion force between microtubules due to these dissociated phosphorylated
taus. We equilibrate upon tau removal using steepest descent relaxation. In the
absence of the depletion force, the transverse rigidity to radial compression
of the bundle falls to zero at about 60% tau occupancy, in agreement with
standard percolation theory results. However, with the attractive depletion
force, spring removal leads to a first order collapse of the bundles over a
wide range of tau occupancies for physiologically realizable conditions. While
our simplest calculations assume a constant concentration of microtubule
intercalants to mediate the depletion force, including a dependence that is
linear in the detached taus yields the same collapse. Applying percolation
theory to removal of taus at microtubule tips, which are likely to be the
protective sites against dynamic instability, we argue that the microtubule
instability can only obtain at low tau occupancy, from 0.06-0.30 depending upon
the tau coordination at the microtubule tips. Hence, the collapse we discover
is likely to be more robust over a wide range of tau occupancies than the
dynamic instability. We suggest in vitro tests of our predicted collapse.Comment: 11 pages, 9 figure
Electrolyte Coatings for High Adhesion Interfaces in Solid-state Batteries from First Principles
We introduce an adhesion parameter that enables rapid screening for materials
interfaces with high adhesion. This parameter is obtained by density functional
theory calculations of individual single-material slabs rather than slabs
consisting of combinations of two materials, eliminating the need to calculate
all configurations of a prohibitively vast space of possible interface
configurations. Cleavage energy calculations are used as an upper bound for
electrolyte and coating energies and implemented in an adapted contact angle
equation to derive the adhesion parameter. In addition to good adhesion, we
impose further constraints in electrochemical stability window, abundance, bulk
reactivity, and stability to screen for coating materials for next-generation
solid-state batteries. Good adhesion is critical in combating delamination and
resistance to Lithium diffusivity in solid-state batteries. Here, we identify
several promising coating candidates for the Li7La3Zr2O12 and sulfide
electrolyte systems including the previously investigated electrode coating
materials LiAlSiO4 and Li5AlO8, making them especially attractive for
experimental optimization and commercialization
Figure 4 Data
<p>These data sets describes curves used in Figure 4 of the PLOS One paper titled: Simulated Cytoskeleton Collapse via tau Degredation by Sendek et al.</p
Figure 5 data
<p>These data sets describes curves used in Figure 5 of the PLOS One paper titled: Simulated Cytoskeleton Collapse via tau Degredation by Sendek et al.</p
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Simulated cytoskeletal collapse via tau degradation.
We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimers disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundles falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06-0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse