Quantifying cell-induced matrix deformation in three dimensions based on imaging matrix fibers

Area of Science:

• Biophysics
• Cell Biology
• Biomaterials Science

Background:

• Cell migration is crucial in development and cancer metastasis, involving movement within 3D fibrous matrices.
• Quantifying the mechanical forces cells exert during migration has been challenging.
• Previous methods relied on indirect observations like matrix remodeling.

Purpose of the Study:

• To develop and apply a novel experimental technique for simultaneously measuring 3D cellular displacements and matrix remodeling.
• To quantify the forces cells generate during invasion of a 3D fibrous matrix.
• To elucidate the mechanisms of cell migration in physiologically relevant environments.

Main Methods:

• A new
• 2-in-1
• experimental technique was developed to capture full-field 3D displacements and matrix structural changes simultaneously.
• Single cells were tracked as they invaded a fibrin matrix.
• Cellular forces were inferred from observed matrix deformation and remodeling.

Main Results:

• Cells were observed to generate tube-like structures within the fibrin matrix.
• These tubular structures were formed through plastic deformation of the matrix.
• Cells subsequently re-used these pre-formed tubes to extend cellular protrusions.
• Both pulling and pushing forces were identified as mechanisms for generating these tubular structures.

Conclusions:

• Cells actively remodel their 3D environment to facilitate migration.
• The formation and reuse of matrix tubes represent a key strategy for cell invasion.
• The developed technique allows for precise quantification of cell-matrix interactions and forces.