Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices

Area of Science:

• Cell Biology
• Biophysics
• Biomaterials Science

Background:

• Collective cell migration is crucial for tissue development, repair, and cancer metastasis.
• The physical forces driving cohesive multicellular movement through dense 3D matrices are not fully understood.

Purpose of the Study:

• To elucidate the physical mechanisms underlying collective cell migration in 3D extracellular matrix (ECM).
• To investigate the role of tensile forces and ECM remodeling in propelling and guiding migrating cell cohorts.

Main Methods:

• Directly observing and quantifying tensile forces at the invasive front of migrating multicellular cohorts.
• Analyzing cell movement correlation and phase with ECM deformations.
• Investigating ECM alignment and microtrack formation induced by cell migration.

Main Results:

• Tensile forces at the invasive front play a dual role: propelling migration and conditioning the matrix.
• These forces trigger mechanosensitive signaling and align the ECM, forming microtracks.
• Cell movements are synchronized with ECM deformations, indicating a coupled dynamic.

Conclusions:

• Collective cell migration in 3D ECM is driven by a dynamic pulling mechanism involving tensile forces.
• Biophysical forces and ECM remodeling are critical regulators of 3D collective cell migration.
• Understanding these mechanisms can inform strategies for controlling tissue remodeling and metastasis.