Self-generated gradients steer collective migration on viscoelastic collagen networks

Area of Science:

• Biophysics
• Cell Biology
• Materials Science

Background:

• Cell migration is crucial for development and disease.
• The physical properties of the cellular microenvironment are known to influence cell migration.
• The role of active physical remodeling by cells in migration dynamics remains poorly understood.

Purpose of the Study:

• To investigate how active physical remodeling by cell clusters affects their migration dynamics on deformable substrates.
• To elucidate the mechanisms underlying self-generated directional migration in the absence of intrinsic cell polarity.

Main Methods:

• Utilizing deformable collagen-I networks as substrates for cell cluster seeding.
• Employing techniques such as traction force microscopy and Brillouin microscopy to analyze cell-substrate interactions.
• Combining experimental observations with theoretical modeling.

Main Results:

• Cell clusters exhibited persistent collective migration on viscoelastic collagen networks.
• Clusters generated transient gradients in collagen density and alignment due to network viscoelastic relaxation.
• Modifications like collagen crosslinking or reduced cluster size decreased network deformation, relaxation time, and gradients, leading to reduced migration persistence.
• Asymmetries in force distribution and collagen stiffness were observed during migration, indicating mechanical cross-talk.

Conclusions:

• Active physical remodeling of the cellular microenvironment by cell clusters can drive persistent collective migration.
• Viscoelastic relaxation of the substrate generates physical cues that promote directional movement.
• This provides a physical model for self-generated directional migration on viscoelastic substrates, independent of intrinsic biochemical polarity cues.