Randomly spread fibroblasts on fibronectin-coated elastomeric membranes respond 
to cyclic strain by a varying degree of focal adhesion assembly and actin 
reorganization. We speculated that the individual shape of the cells, which is 
linked to cytoskeletal structure and pre-stress, might tune these 
integrin-dependent mechanotransduction events. To this aim, fibronectin circles, 
squares and rectangles of identical surface area (2000μm(2)) were micro-contact 
printed onto elastomeric substrates. Fibroblasts plated on these patterns 
occupied the corresponding shapes. Cyclic 10% equibiaxial strain was applied to 
patterned cells for 30min, and changes in cytoskeleton and cell-matrix adhesions 
were quantified after fluorescence staining. After strain, megakaryocytic 
leukemia-1 protein translocated to the nucleus in most cells, indicating 
efficient RhoA activation independently of cell shape. However, circular and 
square cells (with radial symmetry) showed a significantly greater increase in 
the number of actin stress fibers and vinculin-positive focal adhesions after 
cyclic strain than rectangular (bipolar) cells of identical size. Conversely, 
cyclic strain induced larger changes in pY397-FAK positive focal complexes and 
zyxin relocation from focal adhesions to stress fibers in bipolar compared to 
symmetric cells. Thus, radially symmetric cells responded to cyclic strain with 
a larger increase in assembly, whereas bipolar cells reacted with more 
pronounced reorganization of actin stress fibers and matrix contacts. We 
conclude that integrin-mediated responses to external mechanical strain are 
differentially modulated in cells that have the same spreading area but 
different geometries, and do not only depend on mere cell size.