Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices

Area of Science:

• Cell Biology
• Biophysics
• Biomaterials Science

Background:

• Circulating monocytes migrate to tumors, differentiating into pro-tumorigenic macrophages.
• Monocyte migration requires traversing the stiff, viscoelastic tumor microenvironment matrix, primarily composed of type-1 collagen.

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 stromal-like matrices.

Main Methods:

• Utilized interpenetrating networks of type-1 collagen and alginate to create tunable 3D matrices.
• Independently controlled matrix stiffness and stress relaxation (viscoelasticity).
• Cultured and observed monocyte migration within these 3D matrices using advanced microscopy.

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.
• Migration depended on actin polymerization and myosin contractility, not matrix adhesions or Rho-mediated contractility.

Conclusions:

• Matrix stiffness and stress relaxation are critical regulators of monocyte migration into tumors.
• Monocytes employ actin polymerization at the leading edge to generate protrusive forces, creating paths within viscoelastic matrices.