Rapid flow-induced responses in endothelial cells

Endothelial cells alter their morphology, growth rate, and metabolism in re sponse to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescen ce microscopy with optical sectioning, digital imaging, and numerical decon volution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the sa me time frame whole cell height and nuclear height are reduced by about 1 m um. Whole cell height changes may facilitate reduction of shear stress grad ients on the luminal surface, whereas nuclear structural changes may be imp ortant for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been tr eated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilamen ts, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did n ot affect the shear-induced nuclear morphology changes. Colchicine, however , completely abrogated the response, indicating that microtubules may be im plicated in force transmission from the plasma membrane to the nucleus. A p edagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.