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An Efficient and Flexible Cell Aggregation Method for 3D Spheroid Production
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Matrix confinement modulates 3D spheroid sorting and burst-like collective migration.

Grace Cai1, Xinzhi Li2, Shan-Shan Lin3

  • 1Applied Physics Program, University of Michigan, Ann Arbor, MI, USA.

Acta Biomaterialia
|March 15, 2024
PubMed
Summary

Matrix confinement and cell adhesion control tumor cell sorting and invasion. High confinement triggers sorting, while reduced confinement facilitates collective invasion, impacting cancer cell migration.

Keywords:
3D cell cultureCancer invasionCell–cell adhesionHydrogels

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Area of Science:

  • Biophysics
  • Cancer Biology
  • Cellular Mechanics

Background:

  • Tumor microenvironment mechanics influence cancer cell migration.
  • Intercellular interactions in heterogeneous tumors are poorly understood.
  • Physical forces governing cell sorting and invasion in tumors require further investigation.

Purpose of the Study:

  • To explore how matrix confinement influences cell migration in 3D spheroids.
  • To understand the role of physical confinement and cell-cell adhesion in tumor cell sorting and invasion.
  • To investigate the relationship between matrix confinement, cell sorting, and migration dynamics.

Main Methods:

  • Tuning matrix confinement in 3D spheroids to mimic tumor microenvironment changes.
  • Utilizing computational Self-Propelled Voronoi modeling.
  • Investigating tumor cell behavior in co-culture spheroids within collagen-alginate hydrogels of varying stiffness.

Main Results:

  • High matrix confinement induces cell sorting in 3D spheroids.
  • Reduced matrix confinement promotes collective cell invasion after sorting.
  • Spheroids without prior sorting do not exhibit burst-like migration, irrespective of confinement.
  • Spheroid sorting and invasion depend on the balance between cell-generated forces and matrix resistance.

Conclusions:

  • Matrix confinement and intercellular adhesion are key regulators of 3D spheroid dynamics.
  • Findings provide insights into cell sorting and migration mechanisms in primary tumors and metastasis.
  • The study establishes a model where matrix confinement modulates spheroid sorting and unjamming in an adhesion-dependent manner.