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Updated: Jan 14, 2026

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Development of a Microfluidics-Based Approach for Investigating Microtubule Polymer Mechanics

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Stabilizing microtubules increases acute cellular injury at high strain rates

Gia Kang1, Erik Webster1, Daniel Delgado1

  • 1Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada.

Biophysical Journal
|October 22, 2025
PubMed

Insights

Mechanical strain causes mild traumatic brain injury (mTBI). Microtubule stability and Tau phosphorylation influence neuronal damage, suggesting new therapeutic targets for brain injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biomechanics

Background:

  • Mechanical strain is a significant factor in mild traumatic brain injury (mTBI).
  • The precise mechanisms by which strain magnitude and rate affect cellular function in mTBI are not fully understood.
  • The roles of Tau phosphorylation and microtubule stability in neuronal response to mechanical strain require further investigation.

Purpose of the Study:

  • To investigate the acute cellular responses to mechanical strain in SH-SY5Y cells.
  • To elucidate the modulatory roles of Tau phosphorylation and microtubule stability in the context of mTBI.
  • To identify potential therapeutic targets for mitigating TBI-induced neuronal damage.

Main Methods:

  • Utilized a custom cell-stretching system to apply controlled mechanical strain to SH-SY5Y cells.
  • Examined the effects of microtubule-stabilizing (paclitaxel) and destabilizing (nocodazole) agents on cellular membrane damage.
  • Investigated the impact of wild-type Tau overexpression and pharmacological inhibitors of kinases and phosphatases on mTBI outcomes.

Main Results:

  • Increased microtubule (MT) stability exacerbated acute membrane damage, while MT depolymerization reduced it.
  • Overexpression of wild-type Tau worsened cellular injury under mechanical strain.
  • Tau phosphorylation was found to modulate mTBI outcomes, indicating a complex interaction with MT stability.

Conclusions:

  • Microtubule stability and Tau phosphorylation are critical modulators of neuronal injury in response to mechanical strain.
  • Findings suggest a complex interplay between Tau modification and microtubule dynamics in mTBI.
  • This research highlights potential therapeutic strategies targeting Tau phosphorylation and microtubule stability for TBI treatment.

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