Inserted rest period resensitizes MC3T3-E1 cells to fluid shear stress in a time-dependent manner via F-actin-regulated mechanosensitive channel(s)

We report here that the level of endothelin-1 (ET-1) mRNA from bovine aortic endothelial cells grown in vitro is rapidly (within 1 h of exposure) and significantly (fivefold) decreased in response to fluid shear stress of physiological magnitude. The downregulation of ET-1 mRNA occurs in a dose-dependent manner that exhibits saturation above 15 dyn/cm2. The decrease is complete prior to detectable changes in endothelial cell shape and is maintained throughout and following alignment in the direction of blood flow. Peptide levels of ET-1 secreted into the media are also reduced in response to fluid shear stress. Cyclical stretch experiments demonstrated no changes in ET-1 mRNA, while increasing media viscosity with dextran showed that the downregulation is a specific response to shear stress and not to fluid velocity. Although both pulsatile and turbulent shear stress of equal time-average magnitude elicited the same decrease in ET-1 mRNA as steady laminar shear (15 dyn/cm2), low-frequency reversing shear stress did not result in any change. These results show that the magnitude as well as the dynamic character of fluid shear stress can modulate expression of ET-1 in vascular endothelium.

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Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-β receptor and Src

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00434.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. H1081-H1090 ◽

Cited By ~ 11

Author(s):

Shu Q. Liu ◽

Christopher Tieche ◽

Dalin Tang ◽

Paul Alkema

Keyword(s):

Shear Stress ◽

Smooth Muscle ◽

Cell Density ◽

Fluid Shear Stress ◽

Density Gradients ◽

Dependent Manner ◽

Fluid Shear ◽

Polymer Implants ◽

Β Receptor

Blood vessels are subject to fluid shear stress, a hemodynamic factor that inhibits the mitogenic activities of vascular cells. The presence of nonuniform shear stress has been shown to exert graded suppression of cell proliferation and induces the formation of cell density gradients, which in turn regulate the direction of smooth muscle cell (SMC) migration and alignment. Here, we investigated the role of platelet-derived growth factor (PDGF)-β receptor and Src in the regulation of such processes. In experimental models with vascular polymer implants, SMCs migrated from the vessel media into the neointima of the implant under defined fluid shear stress. In a nonuniform shear model, blood shear stress suppressed the expression of PDGF-β receptor and the phosphorylation of Src in a shear level-dependent manner, resulting in the formation of mitogen gradients, which were consistent with the gradient of cell density as well as the alignment of SMCs. In contrast, uniform shear stress in a control model elicited an even influence on the activity of mitogenic molecules without modulating the uniformity of cell density and did not significantly influence the direction of SMC alignment. The suppression of the PDGF-β receptor tyrosine kinase and Src with pharmacological substances diminished the gradients of mitogens and cell density and reduced the influence of nonuniform shear stress on SMC alignment. These observations suggest that PDGF-β receptor and Src possibly serve as mediating factors in nonuniform shear-induced formation of cell density gradients and alignment of SMCs in the neointima of vascular polymer implants.

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Response of osteoblasts to low fluid shear stress is time dependent

Tissue and Cell ◽

10.1016/j.tice.2011.06.003 ◽

2011 ◽

Vol 43 (5) ◽

pp. 311-317 ◽

Cited By ~ 29

Author(s):

Yu Ban ◽

Ying-ying Wu ◽

Tao Yu ◽

Ning Geng ◽

Yong-yue Wang ◽

...

Keyword(s):

Shear Stress ◽

Fluid Shear Stress ◽

Time Dependent ◽

Fluid Shear

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Colonization of distant organs by tumor cells generating circulating homotypic clusters adaptive to fluid shear stress

Scientific Reports ◽

10.1038/s41598-021-85743-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Manabu Maeshiro ◽

Satoru Shinriki ◽

Rin Liu ◽

Yutaka Nakachi ◽

Yoshihiro Komohara ◽

...

Keyword(s):

Shear Stress ◽

Tumor Cells ◽

Fluid Shear Stress ◽

Dna Barcode ◽

Dependent Manner ◽

Fluid Shear ◽

Cortical Actin ◽

Metastatic Recurrence ◽

Static Conditions ◽

E Cadherin

AbstractOnce disseminated tumor cells (DTCs) arrive at a metastatic organ, they remain there, latent, and become seeds of metastasis. However, the clonal composition of DTCs in a latent state remains unclear. Here, we applied high-resolution DNA barcode tracking to a mouse model that recapitulated the metastatic dormancy of head and neck squamous cell carcinoma (HNSCC). We found that clones abundantly circulated peripheral blood dominated DTCs. Through analyses of multiple barcoded clonal lines, we identified specific subclonal population that preferentially generated homotypic circulating tumor cell (CTC) clusters and dominated DTCs. Despite no notable features under static conditions, this population significantly generated stable cell aggregates that were resistant to anoikis under fluid shear stress (FSS) conditions in an E-cadherin-dependent manner. Our data from various cancer cell lines indicated that the ability of aggregate-constituting cells to regulate cortical actin-myosin dynamics governed the aggregates’ stability in FSS. The CTC cluster-originating cells were characterized by the expression of a subset of E-cadherin binding factors enriched with actin cytoskeleton regulators. Furthermore, this expression signature was associated with locoregional and metastatic recurrence in HNSCC patients. These results reveal a biological selection of tumor cells capable of generating FSS-adaptive CTC clusters, which leads to distant colonization.

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Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases

AJP Cell Physiology ◽

10.1152/ajpcell.00358.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. C863-C871 ◽

Cited By ~ 28

Author(s):

Ayako Makino ◽

Michael Glogauer ◽

Gary M. Bokoch ◽

Shu Chien ◽

Geert W. Schmid-Schönbein

Keyword(s):

Signal Transduction ◽

Shear Stress ◽

Fluid Shear Stress ◽

Small Gtpases ◽

Dependent Manner ◽

Fluid Shear ◽

Rho Family

Blood vessels and blood cells are under continuous fluid shear. Studies on vascular endothelium and smooth muscle cells have shown the importance of this mechanical stress in cell signal transduction, gene expression, vascular remodeling, and cell survival. However, in circulating leukocytes, shear-induced signal transduction has not been investigated. Here we examine in vivo and in vitro the control of pseudopods in leukocytes under the influence of fluid shear stress and the role of the Rho family small GTPases. We used a combination of HL-60 cells differentiated into neutrophils (1.4% dimethyl sulfoxide for 5 days) and fresh leukocytes from Rac knockout mice. The cells responded to shear stress (5 dyn/cm2) with retraction of pseudopods and reduction of their projected cell area. The Rac1 and Rac2 activities were decreased by fluid shear in a time- and magnitude-dependent manner, whereas the Cdc42 activity remained unchanged (up to 5 dyn/cm2). The Rho activity was transiently increased and recovered to static levels after 10 min of shear exposure (5 dyn/cm2). Inhibition of either Rac1 or Rac2 slightly but significantly diminished the fluid shear response. Transfection with Rac1-positive mutant enhanced the pseudopod formation during shear. Leukocytes from Rac1-null and Rac2-null mice had an ability to form pseudopods in response to platelet-activating factor but did not respond to fluid shear in vitro. Leukocytes in wild-type mice retracted pseudopods after physiological shear exposure, whereas cells in Rac1-null mice showed no retraction during equal shear. On leukocytes from Rac2-null mice, however, fluid shear exerted a biphasic effect. Leukocytes with extended pseudopods slightly decreased in length, whereas initially round cells increased in length after shear application. The disruption of Rac activity made leukocytes nonresponsive to fluid shear, induced cell adhesion and microvascular stasis, and decreased microvascular density. These results suggest that deactivation of Rac activity by fluid shear plays an important role in stable circulation of leukocytes.

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Fluid shear stress regulates HepG2 cell migration though time-dependent integrin signaling cascade

Cell Adhesion & Migration ◽

10.1080/19336918.2017.1319042 ◽

2017 ◽

Vol 12 (1) ◽

pp. 56-68 ◽

Cited By ~ 5

Author(s):

Hongchi Yu ◽

Yang Shen ◽

Jingsi Jin ◽

Yingying Zhang ◽

Tang Feng ◽

...

Keyword(s):

Shear Stress ◽

Cell Migration ◽

Hepg2 Cell ◽

Fluid Shear Stress ◽

Time Dependent ◽

Integrin Signaling ◽

Signaling Cascade ◽

Fluid Shear

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Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress

AJP Cell Physiology ◽

10.1152/ajpcell.00193.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. C1568-C1575 ◽

Cited By ~ 43

Author(s):

Jhanvi H. Dangaria ◽

Peter J. Butler

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Fluid Shear Stress ◽

Vascular Endothelial Cells ◽

Step Change ◽

Time Dependent ◽

Creep Function ◽

Fluid Shear ◽

Hemodynamic Forces ◽

Forcing Function

Vascular endothelial cells (ECs) respond to temporal and spatial characteristics of hemodynamic forces by alterations in their adhesiveness to leukocytes, secretion of vasodilators, and permeability to blood-borne constituents. These physiological and pathophysiological changes are tied to adaptation of cell mechanics and mechanotransduction, the process by which cells convert forces to intracellular biochemical signals. The exact time scales of these mechanical adaptations, however, remain unknown. We used particle-tracking microrheology to study adaptive changes in intracellular mechanics in response to a step change in fluid shear stress, which simulates both rapid temporal and steady features of hemodynamic forces. Results indicate that ECs become significantly more compliant as early as 30 s after a step change in shear stress from 0 to 10 dyn/cm2followed by recovery of viscoelastic parameters within 4 min of shearing, even though shear stress was maintained. After ECs were sheared for 5 min, return of shear stress to 0 dyn/cm2in a stepwise manner did not result in any further rheological adaptation. Average vesicle displacements were used to determine time-dependent cell deformation and macrorheological parameters by fitting creep function to a linear viscoelastic liquid model. Characteristic time and magnitude for shear-induced deformation were 3 s and 50 nm, respectively. We conclude that ECs rapidly adapt their mechanical properties in response to shear stress, and we provide the first macrorheological parameters for time-dependent deformations of ECs to a physiological forcing function. Such studies provide insight into pathologies such as atherosclerosis, which may find their origins in EC mechanics.

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