Rapid Flow‐Induced Responses in Endothelial Cells

Abstract

Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

Cell-generated traction forces and the resulting matrix deformation modulate microvascular alignment and growth during angiogenesis

“…However, significant gaps remain in our understanding of the mechanisms that determine the spatial organization of angiogenic growth and the topology of the resulting vascular network. Although the role of biochemical factors in angiogenic growth has been studied extensively (1,11,22), very few studies have directly addressed how mechanical factors influence the topology of the vascular network.Mechanical forces affect nearly every aspect of cellular motility, metabolism, proliferation, and differentiation, and presumably the endothelial cells and pericytes that participate in the process of angiogenesis are not excluded from their effects (7,10,21,23,33,35,41). There is a tightly regulated balance between mechanical forces that are applied to the extracellular matrix (ECM) and their effects on endothelial cell phenotype (7,10,18), with the ECM mediating initial cellular mechanotransduction (13).…”

“…Mechanical forces affect nearly every aspect of cellular motility, metabolism, proliferation, and differentiation, and presumably the endothelial cells and pericytes that participate in the process of angiogenesis are not excluded from their effects (7,10,21,23,33,35,41). There is a tightly regulated balance between mechanical forces that are applied to the extracellular matrix (ECM) and their effects on endothelial cell phenotype (7,10,18), with the ECM mediating initial cellular mechanotransduction (13).…”

Unique Morphology and Focal Adhesion Development of Valvular Endothelial Cells in Static and Fluid Flow Environments

“…10,11 Endothelial cells align parallel to the direction of unidirectional flow, through the reorganization of cytoskeletal filaments and focal adhesion complexes. [12][13][14] Fluid flow also induces secretion of vasoactive agents such as nitric oxide and prostaglandin to maintain vessel tone, 15,16 and these processes are regulated by complex signaling events. [17][18][19] Disruption of this signal process, through the oscillation of fluid flow direction 20,21 or signal pathway blockade, inhibits cell alignment, focal adhesion reorganization, and agent release.…”

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

“…The surface topology of each EC is modelled as a sinusoid based on experimental measurements with atomic force microscopy (AFM) of the surfaces of ECs which have not been exposed to shear stress previously [13,62,63]. It has been observed that cell shape can change detectably within 3 min of shear exposure [64], but such changes that reflect biomolecular responses of the cell are not captured in this model. The surface function is given as [62,63] y S ¼ĥ cos (ax) cos (bz), (2:1) whereĥ is the amplitude of the surface contour.…”