Three-dimensional Traction Force Microscopy for Studying Cellular Interactions with Biomaterials

The interactions between biochemical and mechanical signals during cell adhesion, migration, spreading and other processes influence cellular behavior. Three-dimensional measurement techniques are needed to investigate the effect of mechanical properties of the substrate on cellular behavior. This paper discusses a three-dimensional full-field measurement technique that has been developed for measuring large deformations in soft materials. The technique utilizes a digital volume correlation (DVC) algorithm to track motions of sub-volumes within 3-D images obtained using laser scanning confocal microscopy. The technique is well-suited for investigating 3-D mechanical interactions between cells and the extracellular matrix and for obtaining local constitutive properties of soft biomaterials. Results from the migration of single fibroblast cells on polyacrylamide gels and their implications for cell motility models are discussed. The implications that the traction distributions of epithelial cell clusters have on the inhibition of proliferation due to cell contact and scattering of cells in a cluster are discussed. These results provide insights on force fields generated by cells and the role of the mechanical properties of the substrate on cellular interactions and mechanotransduction. Analytical solutions and finite element simulations are used to elucidate the mechanics of cellular forces exerted on the extracellular matrix.