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Microtubule-Based Control of Motor-Clutch System Mechanics in Glioma Cell Migration

Louis S Prahl1, Patrick F Bangasser1, Lauren E Stopfer2

  • 1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Physical Sciences-Oncology Center, University of Minnesota, Minneapolis, MN 55455, USA.

Cell Reports
|November 29, 2018
PubMed

Insights

Microtubule-targeting agents (MTAs) like paclitaxel suppress glioma cell migration by altering cell mechanics. These chemotherapy drugs impact microtubule dynamics and cell traction forces, offering insights into cancer cell movement.

Area of Science:

  • Cell Biology
  • Biophysics
  • Cancer Research

Background:

  • Microtubule-targeting agents (MTAs) are crucial chemotherapy drugs that disrupt microtubule functions.
  • Glioma cells exhibit stiffness-sensitive migration and polarization on compliant substrates.

Purpose of the Study:

  • To investigate the effects of clinically approved MTAs (paclitaxel, vinblastine) on human glioma cell migration and polarization.
  • To elucidate the mechanisms by which MTAs influence cell mechanics, including microtubule dynamics and traction forces.

Main Methods:

  • Utilized compliant hydrogels to study human glioma cell behavior.
  • Administered paclitaxel and vinblastine to assess their impact on cell migration and polarization.
  • Analyzed changes in microtubule dynamics and cell traction forces.
  • Employed computational simulations to model cell migration dynamics.

Main Results:

  • Paclitaxel and vinblastine suppressed stiffness-sensitive migration and polarization of glioma cells.
  • MTAs modulated microtubule dynamics and cell traction forces through distinct mechanisms.
  • Traction force changes were linked to myosin motor activity and adhesion clutch number.
  • Computational models supported the experimental findings, indicating impaired migration with increased protrusion number.

Conclusions:

  • Microtubules play a critical role in controlling cell migration through a signaling-based motor-clutch mechanism.
  • MTAs provide a theoretical framework for understanding how microtubules regulate cell migration and traction forces.
  • The findings offer insights into the mechanisms of action for MTAs in cancer therapy.
Keywords:
actincell migrationcomputational modelingcytoskeletal crosstalkmechanotransductionmicrotubulemicrotubule-targeting agentpaclitaxelreceptor tyrosine kinasevinblastine

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