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Updated: Sep 19, 2025
11:43
Concentric Gel System to Study the Biophysical Role of Matrix Microenvironment on 3D Cell Migration
Published on: April 3, 2015
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Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices
Kolade Adebowale1,2,3, Cole Allan4, Byunghang Ha4
1Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
Summary
Tumor-infiltrating monocytes (immune cells) migrate through stiff, viscous matrices by actin polymerization. Increased matrix stiffness and faster stress relaxation independently enhance this 3D monocyte migration, crucial for tumor progression.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cancer Biology
Background:
- Circulating monocytes infiltrate tumors, differentiating into macrophages that promote tumor progression.
- Monocyte migration to tumors requires traversing the type-1 collagen-rich stromal matrix.
- Tumor stromal matrix exhibits increased stiffness and viscoelasticity compared to normal tissue.
Purpose of the Study:
- To investigate the impact of matrix stiffness and viscoelasticity on three-dimensional (3D) monocyte migration.
- To elucidate the mechanisms underlying monocyte migration through confining viscoelastic matrices.
Main Methods:
- Utilized interpenetrating networks of type-1 collagen and alginate to create tunable stromal-like matrices.
- Cultured monocytes in 3D matrices with independently controlled stiffness and stress relaxation.
- Analyzed monocyte morphology, migration dynamics, and the role of actin polymerization and myosin contractility.
Main Results:
- Increased matrix stiffness and faster stress relaxation independently enhanced 3D monocyte migration.
- Monocytes exhibited amoeboid-like morphology with actin accumulation at the trailing edge.
- Actin polymerization at the leading edge generated protrusive forces, enabling migration through the matrix.
Conclusions:
- Matrix stiffness and stress relaxation are key regulators of monocyte migration.
- Monocyte migration in 3D viscoelastic matrices relies on actin-driven pushing forces.
- Understanding these mechanisms can inform strategies targeting monocyte infiltration in tumors.
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