Morphological responses of endothelial cells to combined fluid shear stress and cyclic strain

Endothelial cells, along with many other cell types, change their morphology when exposed to mechanical stimuli. The morphological responses include reorientation, elongation, and cytoskeletal rearrangement. In response to both cyclic strain and fluid shear stress (FSS), endothelial cells become more elongated and form parallel arrays of actin stress fibers. The reorientation responses of endothelial cells to cyclic strain and FSS are very different—cells align perpendicular to the strain direction and parallel to the FSS direction. Therefore, in straight blood vessels, circumferential deformation and axial FSSact in reinforcing fashion to cause axial alignment of endothelial cells. If circumferential strain were replaced by axial strain, while axial FSS remained, then the combined stimuli would tend to counteract each other. There are, however, few detailed studies of cellular responses to multiple stimuli, and none that have attempted to differentiate the magnitude-dependent responses of these stimuli. Therefore, we investigated the combined effects of applying these stimuli at “equipotent” levels in reinforcing and counteracting fashions. Pure uniaxial cyclic strain of 2% at 1%/sec, steady FSS at 80 dyne/cm2 and pulsatile FS S at 20 ± 10 dyne/cm 2 at 5 dyne/cm2-sec produced the same time course of cell reorientation and were thus deemed “equipotent”.; When pulsatile FSS was applied in a reinforcing manner with cyclic strain, the response appeared to be additive. In contrast, steady FSS and cyclic strain, applied in a reinforcing manner, did not produce such effects. When applied in a counteracting fashion, however, the responses to both pairs of stimuli canceled. In addition to reorientation, we also observed actin stress fibers and cell shape in each case. Individual and reinforcing stimuli resulted in parallel arrays of actin while counteracting stimuli resulted in a random arrangement of actin. Similarly, individual and reinforcing stimuli resulted in cellular elongation while counteracting stimuli canceled cell shape response. These results suggest that the magnitude and direction of cyclic strain and FSS are important determinants, both individually and collectively, of endothelial cell response.