Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Jalali, Sharareh; Tafazzoli-Shadpour, Mohammad; Haghighipour, Nooshin; Omidvar, Ramin; Safshekan, Farzaneh

doi:10.1080/15419061.2016.1265949

Cited by 59 publications

(44 citation statements)

References 48 publications

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“…Several studies have suggested that the regulatory mechanism governing cellular stiffness involves a cell-to-substrate component 6, 7, 44 , as well as cell-to-cell interactions 22 . It has been reported that a non-confluent single cell promotes spreading and enhances cell-substrate interactions by integrin-dependent focal adhesion formation 12 .…”

Section: Discussionmentioning

confidence: 99%

Gap junction-mediated regulation of endothelial cellular stiffness

Okamoto

Kawamoto

Takagi

et al. 2017

Sci Rep

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Endothelial monolayers have shown the ability to signal each other through gap junctions. Gap junction-mediated cell-cell interactions have been implicated in the modulation of endothelial cell functions during vascular inflammation. Inflammatory mediators alter the mechanical properties of endothelial cells, although the exact role of gap junctions in this process remains unclear. Here, we sought to study the role of gap junctions in the regulation of endothelial stiffness, an important physical feature that is associated with many vascular pathologies. The endothelial cellular stiffness of living endothelial cells was determined by using atomic force microscopy. We found that tumor necrosis factor-α transiently increased endothelial cellular stiffness, which is regulated by cytoskeletal rearrangement and cell-cell interactions. We explored the role of gap junctions in endothelial cellular stiffening by utilizing gap junction blockers, carbenoxolone, inhibitory anti-connexin 32 antibody or anti-connexin 43 antibody. Blockade of gap junctions induced the cellular stiffening associated with focal adhesion formation and cytoskeletal rearrangement, and prolonged tumor necrosis factor-α-induced endothelial cellular stiffening. These results suggest that gap junction-mediated cell-cell interactions play an important role in the regulation of endothelial cellular stiffness.

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Section: Discussionmentioning

confidence: 99%

Gap junction-mediated regulation of endothelial cellular stiffness

Okamoto

Kawamoto

Takagi

et al. 2017

Sci Rep

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“…For example, the regulation of endothelial cell properties is not only governed by imposed mechanical forces but also influenced by the stiffness of the substrate to which the endothelial cells are adhered [ 68 ]. Many have improved on the inherently rigid substrate by culturing cells on a thin layer of more compliant material such as functionalised polyacrylamide hydrogels [ 69 ] or polydimethylsiloxane (PDMS) [ 70 ] to imitate the in vivo environment. It is plausible that these techniques could be incorporated into the model by culturing cells on a biomimetic surface within the wells, although no studies have combined the methods to our knowledge.…”

Section: Advantages and Limitations Of The Swirling Well Methodsmentioning

confidence: 99%

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

Warboys¹,

Ghim²,

Weinberg

2019

Atherosclerosis

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A striking feature of atherosclerosis is its highly non-uniform distribution within the arterial tree. This has been attributed to variation in the haemodynamic wall shear stress (WSS) experienced by endothelial cells, but the WSS characteristics that are important and the mechanisms by which they lead to disease remain subjects of intensive investigation despite decades of research. In vivo evidence suggests that multidirectional WSS is highly atherogenic. This possibility is increasingly being studied by culturing endothelial cells in wells that are swirled on an orbital shaker. The method is simple and cost effective, has high throughput and permits chronic exposure, but interpretation of the results can be difficult because the fluid mechanics are complex; hitherto, their description has largely been restricted to the engineering literature. Here we review the findings of such studies, which indicate that putatively atherogenic flow characteristics occur at the centre of the well whilst atheroprotective ones occur towards the edge, and we describe simple mathematical methods for choosing experimental variables that avoid resonance, wave breaking and uncovering of the cells. We additionally summarise a large number of studies showing that endothelium cultured at the centre of the well expresses more pro-inflammatory and fewer homeostatic genes, has higher permeability, proliferation, apoptosis and senescence, and shows more endothelial-to-mesenchymal transition than endothelium at the edge. This simple method, when correctly interpreted, has the potential to greatly increase our understanding of the homeostatic and pathogenic mechanobiology of endothelial cells and may help identify new therapeutic targets in vascular disease.

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“…The cellular Young's modulus was reported as an important mechanical property to reflect the cellular physiological functions (Chen, Xie, Deng, & Yang, ; Jalali et al, ). Recent supporting works also claimed that the cellular Young's modulus could be expected to facilitate the search for biomarkers related to disease diagnosis progress and treatment (Calvo et al, ; Yang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus

Xia

Zhao

Liu

et al. 2018

Journal Cellular Physiology

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Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness-controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver. Three levels of stiffness were used in our experiment that corresponded to the stiffness levels found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37 kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by substrate stiffness. Soft substrate promoted the cellular migration and directionality. The cellular Young's modulus firstly increased and then decreased with increasing substrate stiffness. Integrin-β1 and β-catenin expression on cytomembrane were up-regulated and down-regulated with the increase of substrate stiffness, respectively. Our data not only suggested that hepatocytes were sensitive to substrate stiffness, but also suggested that there may be a potential relationship among substrate stiffness, cellular Young's modulus and the dynamic balance of integrin-β1 and β-catenin pathways. These results may provide us a new insight in mechanism investigation of mechano-dependent diseases, especially like fibrosis related diseases.

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Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Cited by 59 publications

References 48 publications

Gap junction-mediated regulation of endothelial cellular stiffness

Gap junction-mediated regulation of endothelial cellular stiffness

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus

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