Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments

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.