unchanging ECM stiffness. In fact, while some individual focal adhesions may display stable traction forces, others exhibit tugging traction in the manner of a repeated cycle of tugging and release. The properties of focal adhesions - whether stable or tugging - are independent of their neighbors and as such, each focal adhesion acts autonomously. This tugging traction has been shown to be dispensable to other forms of cell migration, such as chemotaxis and haptotaxis, but required for durotaxis. The focal adhesion proteins (FAK/paxillin/vinculin) - and their phosphorylation-dependent interactions as well as their asymmetrical distribution within the cell (i.e. YAP activation and nuclear translocation via stiffness activated pFAK) - are required in order to exhibit high traction and tugging traction across a wide range of ECM rigidities. Furthermore, a reduction in focal adhesion tension by transferring cells to softer ECM or by inhibiting ROCK results in focal adhesion switching from stable to tugging states. Thus, rigidity mechanosensing allows a cell to sample matrix stiffness at the resolution of focal adhesion spacing within a cell (≈1-5μm). The integration of biochemical and mechanical cues may allow fine-tuning of cell migration. However, the physiological reasoning behind durotaxis—and specifically the tendency of cells to migrate up rigidity gradients—is unknown. Measuring traction The most prevalent and accurate modern method for measuring the traction forces that cells exert on the substrate relies on traction force microscopy (TFM). The principle behind this method is to measure deformation in the substrate by calculating 2-dimensional displacement of fluorescent beads that are embedded in the matrix. High-resolution TFM allows the analysis of traction forces at much smaller structures, such as focal adhesions, at a spatial resolution of ~1 μm. Clinical significance The role of durotaxis under physiological conditions remains unknown. It may serve a purpose in fine-tuning the movement response of a cell to extracellular biochemical cues, though the relative contribution of durotaxis in a physiological environment where a cell is subject to other taxes (e.g. chemotaxis) is unknown, and may in fact prove to be wholly dispensable for cell migration in vivo. The phenomenon might also have a role in several disease states that include the stiffening of tissues, as outlined below. Cancer It is a common observation that tumors are stiffer than the surrounding tissue, and even serves as the basis for breast cancer self-examination. In fact, breast cancer tissue has been reported to be as much as ten