Probing mechanical forces in curvature-sensitive cell adhesions

Abstract

Integrin-mediated focal adhesions facilitate mammalian cell adhesion to the extracellular matrix (ECM), a topologically complex network of protein fibers. While extensive studies on cellular adhesion to the ECM have been done, outstanding questions remain regarding the relationship between three-dimensional (3D) ECM geometry and cellular adhesion, namely how the physical properties of the 3D ECM affect cellular mechanotransduction. To probe this relationship, we used a quartz nanostructure platform to induce different curvature geometries in cells and found that cells exhibit curvature-induced adhesions. Since the formation of focal adhesions is tied to mechanical cues in the environment, we then explored whether mechanical forces are involved in these curvature-sensitive adhesions. We utilized two genetically encoded, FRET-based talin tension biosensors, one sensitive to forces in the range of 3-5 pN and the other sensitive to forces in the range of 9-11 pN. Using ratiometric imaging, we then compared these adhesions with focal adhesions and found that while these curvature-sensitive adhesions bear mechanical forces, they experience lower tension compared to focal adhesions. In this study, we aim to further explore the intra- and extracellular forces involved in these curvature-sensitive adhesions.