Motility Patterns of Cultured Endothelial Cells Exposed to Physiological Levels of Fluid Shear Stress a

Fluid shear stress affects the shape, alignment, and cytoskeletal organization of vascular endothelial cells (EC) in situ and in vitro.'-' We used cultured EC exposed to various levels of fluid shear stress as a model system for investigating how cells respond to mechanical forces. Using an optical flow chamber system," we analyzed the motility pattern of EC and vascular smooth muscle cells (SMC) exposed to physiological levels of fluid shear stress. When confluent bovine or canine arterial EC grown on type-I collagen-coated glass surface were exposed to 6-11 dynes/cmz (high shear) for over 36 h, the long axes of the EC and their stress fibers became aligned parallel to the direction of flow. Migration of EC biased preferentially in the downstream direction was apparent immediately after exposure to these levels of shear stress. With 4 dynes/cm* or less, they did not align or move in the direction of flow. EC in sparse culture did not show these morphological changes even after exposure to the high shear level for 100 hours. After transition from a low shear to a high shear condition, however, sparsely cultured EC extended lamellipodia predominantly on the downstream side and began to migrate preferentially downstream. SMC in sparse or subconfluent cultures did not align or migrate in the direction of flow with shear stress levels of up to 10 dynes/cm2. These results show that the motility pattern of a single EC, but not an SMC, can rapidly be affected by fluid shear stress and that the parallel orientation of the major axis of EC induced by high shear may require cell-cell interaction. An analysis of the cell trails of sparsely cultured EC is summarized in TABLE 1 and suggests a possible mechanism for the biased cell locomotion observed under the high shear conditions. Consistent with a random walk model, EC exposed to low shear stress moved in all directions with the same velocity, and the magnitude of the turns was independent of the direction of cell movement. Although EC locomotion was slightly accelerated under high shear stress in the direction of flow, this level of acceleration could not account for the biased migration of EC under high shear.