Cells generate mechanical forces (traction forces, TFs) while interacting with the extracellular matrix or neighbouring cells. Forces are generated by both cells and extracellular matrix (ECM) and transmitted within the cell-ECM or cell-cell contacts involving focal adhesions or adherens junctions. Within more than two decades, substantial progress has been achieved in techniques that measure TFs. One of the techniques is traction force microscopy (TFM). This review discusses the TFM and its advances in measuring TFs exerted by cells (single cells and multicellular systems) at cell-ECM and cell-cell junctional intracellular interfaces. The answers to how cells sense, adapt and respond to mechanical forces unravel their role in controlling and regulating cell behaviour in normal and pathological conditions.

The identification of cancer-related changes in cells and tissues based on the measurements of elastic properties using atomic force microscopy (AFM) seems to be approaching clinical application. Several limiting aspects have already been discussed; however, still, no data have shown how specific AFM probe geometries are related to the biomechanical evaluation of cancer cells. Here, we analyze and compare the nanomechanical results of mechanically homogenous polyacrylamide gels and heterogeneous bladder cancer cells measured using AFM probes of various tip geometry, including symmetric and non-symmetric pyramids and a sphere. Our observations show large modulus variability aligned with both types of AFM probes used and with the internal structure of the cells. Altogether, these results demonstrate that it is possible to differentiate between compliant and rigid samples of kPa elasticity; however, simultaneously, they highlight the strong need for standardized protocols for AFM-based elasticity measurements if applied in clinical practice including the use of a single type of AFM cantilever.