scholarly journals The Cycling of Intracellular Calcium Released in Response to Fluid Shear Stress Is Critical for Migration-Associated Actin Reorganization in Eosinophils

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 157
Author(s):  
Kiho Son ◽  
Amer Hussain ◽  
Roma Sehmi ◽  
Luke Janssen
Keyword(s):  
Shear Stress ◽  
Calcium Signaling ◽  
Intracellular Calcium ◽  
Actin Polymerization ◽  
Calcium Release ◽  
Fluid Shear Stress ◽  
Morphological Changes ◽  
Calcium Flux ◽  
Fluid Shear ◽  
The Impact

The magnitude of eosinophil mobilization into respiratory tissues drives the severity of inflammation in several airway diseases. In classical models of leukocyte extravasation, surface integrins undergo conformational switches to high-affinity states via chemokine binding activation. Recently, we learned that eosinophil integrins possess mechanosensitive properties that detect fluid shear stress, which alone was sufficient to induce activation. This mechanical stimulus triggered intracellular calcium release and hallmark migration-associated cytoskeletal reorganization including flattening for increased cell–substratum contact area and pseudopodia formation. The present study utilized confocal fluorescence microscopy to investigate the effects of pharmacological inhibitors to calcium signaling and actin polymerization pathways on shear stress-induced migration in vitro. Morphological changes (cell elongation, membrane protrusions) succeeded the calcium flux in untreated eosinophils within 2 min, suggesting that calcium signaling was upstream of actin cytoskeleton rearrangement. The inhibition of ryanodine receptors and endomembrane Ca2+-ATPases corroborated this idea, indicated by a significant increase in time between the calcium spike and actin polymerization. The impact of the temporal link is evident as the capacity of treated eosinophils to move across fibronectin-coated surfaces was significantly hampered relative to untreated eosinophils. Furthermore, we determined that the nature of cellular motility in response to fluid shear stress was nondirectional.

Fluid shear stress induces actin polymerization in human neutrophils

1996 ◽  
Vol 63 (4) ◽  
pp. 432-441 ◽  
Author(s):  
Masaki Okuyama ◽  
Yoshihiko Ohta ◽  
Jun-ichi Kambayashi ◽  
Morito Monden
Keyword(s):  
Shear Stress ◽  
Actin Polymerization ◽  
Fluid Shear Stress ◽  
Human Neutrophils ◽  
Fluid Shear

Role of p120-catenin in the morphological changes of endothelial cells exposed to fluid shear stress

2010 ◽  
Vol 398 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Naoya Sakamoto ◽  
Kei Segawa ◽  
Makoto Kanzaki ◽  
Toshiro Ohashi ◽  
Masaaki Sato
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Morphological Changes ◽  
Fluid Shear ◽  
P120 Catenin

Simultaneous Measurement of Morphology and Traction Forces of Endothelial Cells Under Fluid Shear Stress

2012 ◽  
Author(s):  
Toshiro Ohashi ◽  
Yusaku Niida ◽  
Ryoichi Tanaka ◽  
Masaaki Sato
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cells ◽  
Morphological Changes ◽  
Traction Force ◽  
Flow Chamber ◽  
Fluid Shear ◽  
Traction Forces ◽  
Contractile Forces

Under fluid shear stress, vascular endothelial cells (ECs) cultured in a monolayer are known to exhibit marked elongation and orientation to the direction of flow [1]. It is also observed that intracellular F-actin filament distributions changed depending on the amplitude of shear stress and the direction of flow, suggesting morphology of ECs is closely related to cytoskeltal structure [2]. ECs generate contractile forces by the actin-myosin machinery and the forces are transmitted to underlying substrate as cellular traction forces. We hypothesize that reorganization of cytoskeletal structures regulates traction forces in ECs exposed to fluid shear stress. In order to measure traction forces and cell morphology simultaneously, we have developed a newly designed flow-imposed device in which a substrate with arrays of elastomeric micropillars (3 μm in diameter and 10 μm in height) is integrated on the bottom of a parallel plate flow chamber. In this study, traction force distributions and morphological changes in GFP-tagged ECs in a monolayer under fluid flow are simultaneously evaluated through image analysis in a spatial and a temporal manner.

Fluid shear stress combined with shear stress spatial gradients regulates vascular endothelial morphology

2017 ◽  
Vol 9 (7) ◽  
pp. 584-594 ◽  
Author(s):  
Daisuke Yoshino ◽  
Naoya Sakamoto ◽  
Masaaki Sato
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Endothelial Cell ◽  
Fluid Shear Stress ◽  
Morphological Changes ◽  
Vascular Endothelial ◽  
Fluid Shear ◽  
Spatial Gradients ◽  
The Relationship

The magnitude of the relationship between shear stress (SS) and SS gradient plays an important role in regulating endothelial cell (EC) polarity and the resulting morphological changes in ECs in response to fluid flow.

scholarly journals Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emily J. Ross ◽  
Emily R. Gordon ◽  
Hanna Sothers ◽  
Roshan Darji ◽  
Oakley Baron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Proximal Tubule ◽  
Fluid Shear Stress ◽  
Renal Diseases ◽  
Genome Wide Association Studies ◽  
Fluid Shear ◽  
Biologically Relevant ◽  
Tubule Cells ◽  
The Impact

AbstractThe kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.

scholarly journals Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis

2021 ◽  
Author(s):  
Stefan Offermanns ◽  
ShengPeng Wang ◽  
Yue Shi ◽  
Tanja Moeller ◽  
Rebekka Stegmeyer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Actin Polymerization ◽  
Fluid Shear Stress ◽  
Endothelial Barrier ◽  
Low Flow ◽  
Intercellular Adhesion Molecule ◽  
Fluid Shear ◽  
Downstream Signaling ◽  
Signaling Events

Abstract The extravasation of leukocytes is a critical step during inflammation which requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells. It is still unclear how these initial processes induce downstream signaling events resulting in the opening of inter-endothelial junctions to allow leukocyte diapedesis. Here we show that mechanical forces induced by leukocyte-induced clustering of ICAM-1 and fluid shear stress exerted by the flowing blood synergistically activate the mechanosensitive cation channel PIEZO1 in endothelial cells. In human and mouse endothelial cells exposed to low flow, PIEZO1 mediates leukocyte-induced increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of SRC, PYK2 and myosin light chain (MLC) leading to endothelial barrier opening. Mice with endothelium-specific loss of Piezo1 show decreased leukocyte extravasation in different inflammation models. We found that actin polymerization and actomyosin contraction induced by ICAM-1 clustering synergistically with fluid shear stress increase endothelial plasma membrane tension to activate PIEZO1. Our data reveal a mechanism by which leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis.

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