ArticleBiophysical journal2014
Viscoelasticity of tau proteins leads to strain rate-dependent breaking of microtubules during axonal stretch injury: predictions from a mathematical model.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
- A model of axonal damage accumulation from real-world head impact exposure.Annals of biomedical engineering · 2026Article
- Neuromechanobiology: Bridging Mechanobiology and Neuroscience Through Evidence and Open Questions.Cells · 2026Review
- Cellular mechanisms of traumatic brain injury.npj biological physics and mechanics · 2025Review
- Anatomical Features and Material Properties of Human Surrogate Head Models Affect Spatial and Temporal Brain Motion under Blunt Impact.Bioengineering (Basel, Switzerland) · 2024Article
- Sex differences in the extent of acute axonal pathologies after experimental concussion.Acta neuropathologica · 2024Article
- Stretch-Induced Injury Affects Cortical Neuronal Networks in a Time- and Severity-Dependent Manner.Annals of biomedical engineering · 2024Article
- DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome-Lysosome Fusion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Can repetitive mechanical motion cause structural damage to axons?Frontiers in molecular neuroscience · 2024Review
- Identifying the Phenotypes of Diffuse Axonal Injury Following Traumatic Brain Injury.Brain sciences · 2023Review
- Characterization of neural mechanotransduction response in human traumatic brain injury organoid model.Scientific reports · 2023Article
- Mild traumatic brain injury as a pathological process.Heliyon · 2023Review
- Cooperative melting in double-stranded peptide chains through local mechanical interactions.Journal of the Royal Society, Interface · 2023Article
- Image-based axon model highlights heterogeneity in initiation of damage.Biophysical journal · 2023Article
- Axonal transport during injury on a theoretical axon.Frontiers in cellular neuroscience · 2023Article
- Cavitation induced fracture of intact brain tissue.Biophysical journal · 2022Article
- Escalation of Tau Accumulation after a Traumatic Brain Injury: Findings from Positron Emission Tomography.Brain sciences · 2022Article
- Cross-linkers at growing microtubule ends generate forces that drive actin transport.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Blood Biomarkers in Brain Injury Medicine.Current physical medicine and rehabilitation reports · 2022Article
- Viscoelastic damage evaluation of the axon.Frontiers in bioengineering and biotechnology · 2022Article
- Effect of Velocity and Contact Stress Area on the Dynamic Behavior of the Spinal Cord Under Different Testing Conditions.Frontiers in bioengineering and biotechnology · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
The unique viscoelastic nature of axons is thought to underlie selective vulnerability to damage during traumatic brain injury. In particular, dynamic loading of axons has been shown to mechanically break microtubules at the time of injury. However, the mechanism of this rate-dependent response has remained elusive. Here, we present a microstructural model of the axonal cytoskeleton to quantitatively elucidate the interaction between microtubules and tau proteins under mechanical loading. Mirroring the axon ultrastructure, the microtubules were arranged in staggered arrays, cross-linked by tau proteins. We found that the viscoelastic behavior specifically of tau proteins leads to mechanical breaking of microtubules at high strain rates, whereas extension of tau allows for reversible sliding of microtubules without any damage at small strain rates. Based on the stiffness and viscosity of tau proteins inferred from single-molecule force spectroscopy studies, we predict the critical strain rate for microtubule breaking to be in the range 22-44 s(-1), in excellent agreement with recent experiments on dynamic loading of micropatterned neuronal cultures. We also identified a characteristic length scale for load transfer that depends on microstructural properties and have derived a phase diagram in the parameter space spanned by loading rate and microtubule length that demarcates those regions where axons can be loaded and unloaded reversibly and those where axons are injured due to breaking of the microtubules.
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