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Concentric Gel System to Study the Biophysical Role of Matrix Microenvironment on 3D Cell Migration
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Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments.

Katrina M Wisdom1, Kolade Adebowale2, Julie Chang3

  • 1Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA.

Nature Communications
|October 10, 2018
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Summary

Cancer cells can migrate through confining matrices by deforming them. This study reveals a new protease-independent migration mode where cells use invadopodia to create channels in plastic materials.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Biomaterials Science

Background:

  • Cancer cell migration occurs via protease-dependent or -independent routes.
  • Confining matrices like basement membranes (BMs) often pose migration barriers.
  • Extracellular matrices can possess viscoelasticity and mechanical plasticity, altering pore size.

Purpose of the Study:

  • To investigate the impact of matrix plasticity on cancer cell migration.
  • To explore a novel mode of cell migration through malleable nanoporous materials.

Main Methods:

  • Development of interpenetrating network (IPN) hydrogels with tunable plasticity, independent of stiffness.
  • Presentation of basement membrane (BM) ligands on hydrogels.
  • Observation and analysis of cancer cell migration within these engineered matrices.

Main Results:

  • Cancer cells in high plasticity IPNs exhibited protease-independent migration.
  • Cells extended invadopodia to mechanically and plastically open micron-sized channels.
  • This facilitated migration through otherwise confining nanoporous structures.

Conclusions:

  • A new mode of protease-independent cancer cell migration has been discovered.
  • Matrix mechanical plasticity enables cells to create their own migration pathways.
  • This finding is relevant for understanding cell movement in complex biological environments.