A device for dynamic modulation of cell-generated tension in 3D biopolymer gels

The mechanical environment surrounding cells has a critical impact on their behavior, including differentiation, migration, shape and proliferation. Studies have shown that substrate stiffness plays a key role in the behavior of cells grown on 2D substrates, and substrates with dynamic modulus. However, methods for studying cellular response to active changes in stiffness in 3D are lacking. The goal of this project was to develop a method to mechanically modulate the boundary stiffness experienced by fibroblasts in a 3D gel to mimic extracellular matrix. We created a device that utilizes thin stainless steel cantilevered beams that support cell-seeded gels suspended within a culture well. The boundary stiffness is dynamically modulated by a clamp which changes the active length of the cantilever beams. The tensile forces generated by the cells can be quantified based on the calculated spring constant for the active length of the particular set of beams and the subsequent deflection of the beams from cellular contraction of the collagen gel. Spring constants at various clamp heights were validated using force vs. displacement testing of the prototype. In future experiments, collagen gels populated with cells will be grown around the end of the beams, tension will be quantified based on deflection, and active length will be actuated to observe changes in gel contraction, cell proliferation and differentiation. This device has the potential to add significantly to our knowledge of how cells respond to changes in their mechanical environment.