A novel method for sensor-based quantification of single/multicellular force dynamics and stiffening in 3D matrices

Area of Science:

• Cellular Mechanics
• Biomaterials Science
• Biophysics

Background:

• Cells exert mechanical forces on their 3D extracellular matrix (ECM) and neighbors.
• Cellular forces and biochemical signals dynamically remodel the ECM, influencing cell behavior.
• Existing methods lack the ability to quantify single-cell forces and ECM remodeling in 3D.

Purpose of the Study:

• To introduce a novel method for quantifying single-cell forces and 3D matrix remodeling.
• To enable direct measurement of cell-generated forces and concurrent matrix stiffness changes.
• To provide a tool for studying cell-ECM mechanical reciprocity in complex 3D environments.

Main Methods:

• Development of a high-resolution microfabricated sensor for 3D cell-ECM tissue.
• Utilized self-assembled 3D cell-ECM constructs on the sensor.
• Measured single and multicellular force dynamics and tissue stiffness with 1-nN resolution.

Main Results:

• Demonstrated the ability to measure single-cell force fluctuations in 3D.
• Quantified multicellular force dynamics of fibroblasts, cancer cells, and cancer-associated fibroblasts.
• Observed a threefold increase in tissue stiffness within 24 hours in a cancer cell/fibroblast co-culture model.

Conclusions:

• The developed sensor successfully quantifies single-cell forces and 3D matrix remodeling.
• This technology provides new insights into the dynamic interplay between cells and their microenvironment.
• The findings highlight the significant matrix remodeling capabilities of cancer cells and associated fibroblasts in a 3D context.