Simulated cytoskeletal collapse via tau degradation

Area of Science:

• Biophysics
• Neuroscience
• Cell Biology

Background:

• Microtubule-tau bundles are crucial for neuronal axon stability.
• Loss of tau proteins is a hallmark of neurodegenerative diseases like Alzheimer's disease.
• Existing models do not fully capture the mechanical consequences of tau detachment.

Purpose of the Study:

• To develop a mechanical model of microtubule-tau bundles.
• To investigate the effects of tau removal on bundle stability.
• To explore the role of tau phosphorylation and potential depletion forces.

Main Methods:

• A coarse-grained, 2D mechanical model of microtubule-tau bundles.
• Modeling taus as entropic springs between microtubules.
• Simulating tau removal via phosphorylation and incorporating a depletion force.
• Using steepest descent relaxation for equilibration.

Main Results:

• Without depletion forces, bundle rigidity to radial compression vanishes at ~60% tau occupancy.
• With an attractive depletion force, tau removal causes a first-order bundle collapse over a wide tau occupancy range.
• The predicted collapse is more robust than microtubule dynamic instability.

Conclusions:

• Tau detachment can lead to a significant collapse of microtubule bundles in axons.
• This collapse mechanism is a potential contributor to neurodegeneration.
• The findings suggest in vitro experiments to validate the predicted collapse phenomenon.