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 (...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4146510?pdf=render |
| _version_ | 1811235734935306240 |
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| author | Austin Sendek Henry R Fuller N Robert Hayre Rajiv R P Singh Daniel L Cox |
| author_facet | Austin Sendek Henry R Fuller N Robert Hayre Rajiv R P Singh Daniel L Cox |
| author_sort | Austin Sendek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T11:56:37Z |
| format | Article |
| id | doaj.art-1000eb0db8ea43de9f6276c2e67645d9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T11:56:37Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1000eb0db8ea43de9f6276c2e67645d92022-12-22T03:33:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10496510.1371/journal.pone.0104965Simulated cytoskeletal collapse via tau degradation.Austin SendekHenry R FullerN Robert HayreRajiv R P SinghDaniel L CoxWe 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.http://europepmc.org/articles/PMC4146510?pdf=render |
| spellingShingle | Austin Sendek Henry R Fuller N Robert Hayre Rajiv R P Singh Daniel L Cox Simulated cytoskeletal collapse via tau degradation. PLoS ONE |
| title | Simulated cytoskeletal collapse via tau degradation. |
| title_full | Simulated cytoskeletal collapse via tau degradation. |
| title_fullStr | Simulated cytoskeletal collapse via tau degradation. |
| title_full_unstemmed | Simulated cytoskeletal collapse via tau degradation. |
| title_short | Simulated cytoskeletal collapse via tau degradation. |
| title_sort | simulated cytoskeletal collapse via tau degradation |
| url | http://europepmc.org/articles/PMC4146510?pdf=render |
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