In our organism, cells are embedded in three-dimensional (3D) extracellular matrices (ECM) with highly inhomogeneous material properties. To migrate through the ECM, cells deform the ECM in all spatial directions by applying 3D traction forces. Additionally, many cell types can dynamically reinforce the ECM by secreting matrix proteins, or degrade it by secreting proteolytic enzymes. Despite the complexity of these cell-ECM interactions, most in vitro studies performed in the last two decades have measured two-dimensional (2D) traction forces on substrata of constant mechanical properties. Thus, there is a demand for novel assays and analyses that can probe cell-ECM mechanical stress interactions in more realistic cellular environments.
This talk will summarize our recent advances in the development of traction force microscopy (TFM) techniques for 3D ECMs with either constant or spatially varying mechanical properties. We will also illustrate the practical application of these methods to determine cell-ECM mechanical stresses in relevant biological processes such as cancer cell invasion into 3D ECMs, and cell-cell mechanical forces during the transendothelial migration of leukocytes.