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Matrix rigidity regulates microtubule network polarization in migration.

Matthew Raab1, Dennis E Discher1,2,3

  • 1Molecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA.

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Extracellular matrix stiffness influences microtubule organizing center (MTOC) positioning during cell migration. Stiff matrices promote MTOC polarization in front of the nucleus, crucial for cell migration and polarization.

Keywords:
matrix stiffnessmicrotubulesmigrationpolarity

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Area of Science:

  • Cell Biology
  • Biophysics
  • Mechanobiology

Background:

  • The microtubule organizing center (MTOC) plays a critical role in cell polarization and migration.
  • Previous studies have shown conflicting evidence regarding MTOC localization in migratory cells.

Purpose of the Study:

  • To investigate the role of extracellular matrix (ECM) stiffness in modulating MTOC subcellular localization during cell migration.
  • To understand how ECM stiffness influences microtubule organization and cell polarization.

Main Methods:

  • Utilized scratch wound assays and single-cell migration of mesenchymal stem cells (MSCs) on substrates of varying stiffness.
  • Observed MTOC and microtubule density localization relative to the nucleus.
  • Examined cell behavior on immobilized micro-patterns of different stiffness during interphase and cytokinesis.

Main Results:

  • MTOC localization was random on soft matrices but polarized anterior to the nucleus on stiff matrices during cell migration.
  • Microtubule density mirrored MTOC polarization, being anterior on stiff matrices and random on soft matrices.
  • During cytokinesis, centrosome polarization occurred regardless of matrix stiffness, but MIIB localization in the cleavage furrow was affected by matrix softness.

Conclusions:

  • Cell migration is essential for orienting the MTOC anterior to the nucleus.
  • Extracellular matrix stiffness is a key factor driving cell polarization during migration.
  • MTOC positioning is dynamically regulated by both cell migration and substrate mechanics.