Shear stress modulates endothelial cell morphology and F‐actin organization through the regulation of focal adhesion‐associated proteins

Abstract

Flow-related shear stress has been shown to modulate endothelial cell structure and function including F-actin microfilament organization. Focal adhesion-associated proteins such as vinculin, talin, and specific integrins may play a role in the modulation of these cytoskeletal and morphological changes. Double-label immunofluorescence studies indicated that, in static culture, alpha 5 beta 1 fibronectin receptors (alpha 5 beta 1 FNRs) and alpha v beta 3 vitronectin receptors (alpha v beta 3 VNRs) were found predominantly in the peripheral regions of bovine aortic endothelial cells (BAECs) corresponding to the localization of vinculin, talin, and actin microfilament terminations. In response to shear stress, concomitant with cell elongation and the appearance of stress fibers aligned with the direction of flow, there was a prominent localization of vinculin and alpha v beta 3 VNRs as the "upstream" end of the cells. Stress fiber terminations were clearly evident at these concentrations of focal adhesion-associated proteins. These data suggest that the upstream concentration of these proteins may direct shear stress-induced stress fiber formation and may function in the alignment of the fibers in the direction of flow. Levels of surface alpha v beta 3 VNRs were found to decrease in response to flow, possibly reflecting the decrease in numbers of "downstream" receptors. Unlike the arrangement of vinculin and alpha v beta 3 VNRs observed following exposure to flow, talin and alpha 5 beta 1 FNRs, in addition to being localized at the upstream end of the cell, were also evenly distributed throughout the rest of the cell. Surface levels of alpha 5 beta 1 FNRs increased in response to shear stress, perhaps providing an increased adherence of BAECs to the extracellular matrix through these receptors. These data suggest that focal adhesion-associated proteins play specific roles in the response of BAECs to shear stress.

Effect of cyclic strain and plating matrix on cell proliferation and integrin expression by ligament fibroblasts

“…Several studies have suggested that strain increases cell proliferation by increasing autocrine production of PDGF. 7,32 With avian tendon cells, however, synergistic action of both load and PDGF is required for enhancement of cellular proliferation. 33 Several cytokines have been shown to stimulate cell proliferation [34][35][36][37][38] and cell migration 35 of ACL and MCL cells.…”

“…1,2 Application of mechanical load also influences cell proliferation, differentiation, and gene expression in a wide variety of cells; [3][4][5][6][7][8][9][10][11][12][13] however, the molecular mechanisms have not been well defined. Mechanical deformation of the cell or matrix is sensed by specific interactions between extracellular matrix molecules and membrane proteins including the family of transmembrane proteins known as integrins.…”

Focal Expression of Angiotensin II Type 1 Receptor and Smooth Muscle Cell Proliferation in the Neointima of Experimental Vein Grafts

“…34 -42 For instance, altered fluid shear stress influences the activities of mitogen-activated protein kinases 43,44 and G proteins, 45 the production rate of prostacyclin, 46 the activities of growth factors, 26,33,35,47,48 and the morphology 49,50 and cytoskeletal structure 51 of endothelial cells. These changes have been implicated in the mediation of mechanical stress-related vascular atherogenesis.…”

Biomimetic study of rolling transport through smooth muscle contraction

“…While it is clear that the transport of oosperm involves smooth muscle contraction [1,2], the detailed mechanism still remains elusive [1][2][3][4][5][6][7], due in part to the complexity of cellsubstrate interactions via receptor-ligand binding as well as various physical forces inside and outside of the cytoskeleton [8][9][10][11][12]. Cells are known to respond to mechanical forces exerted through surrounding fluid, adhering beads or substrates [9,[12][13][14], and they could detach, slip or roll on a substrate in response to these forces [15][16][17][18][19][20][21][22]. For example, cells on a cyclically stretched substrate tend to reorient themselves away from the stretching direction [23][24][25][26][27], and cells migrate along a substrate with rigidity gradient (durotaxis) [18].…”