Focal adhesions (FAs) and their regulation are instrumental in cellular processes, such as migration, spreading and differentiation. Both chemical and mechanical cues have been attributed with regulating the assembly and dynamics of this type of extracellular matrix (ECM) adhesion. However, unlike the well-studied mechano-responsiveness of FAs, the response of elongated fibrillar adhesions to such cues remains unclear. In this study, Johanna Ivaska and colleagues (Barber-Perez et al., 2020) now address the susceptibility of fibrillar adhesions to changes in ECM elasticity. To that end, they first fabricate an easy-to-reproduce and low-cost thin hydrogel that includes fluorescently labelled beads and is compatible with high-resolution imaging. By allowing soft and stiff hydrogels to diffuse and polymerise, gradients of stiffness could be generated, and the density of fluorescent beads allowed an approximation of the stiffness without the need to explicitly measure it by atomic force microscopy. The authors then identified active α5β1-integrin as an ideal fibrillar adhesion marker and, using this marker, observed that the length of fibrillar adhesions positively correlated with substrate stiffness. This tensin-dependent lengthening of fibrillar adhesions might have implications in tissue fibrosis and cancer. Furthermore, the method to generate gradient gels presented here provides a new addition to the cell biologist's toolbox to study mechano-responsiveness.
