scholarly journals Mechanotransmission in endothelial cells subjected to oscillatory and multi-directional shear flow

2017 ◽  
Vol 14 (130) ◽  
pp. 20170185 ◽  
Author(s):  
Mahsa Dabagh ◽  
Payman Jalali ◽  
Peter J. Butler ◽  
Amanda Randles ◽  
John M. Tarbell

Local haemodynamics are linked to the non-uniform distribution of atherosclerosic lesions in arteries. Low and oscillatory (reversing in the axial flow direction) wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs) mediating disease localization. The objective of this study is to investigate computationally how the flow direction (reflected in WSS variation on the EC surface over time) influences the forces experienced by structural components of ECs that are believed to play important roles in mechanotransduction. A three-dimensional, multi-scale, multi-component, viscoelastic model of focally adhered ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel to the principal flow direction, or multi-directional oscillatory WSS with reversing axial and transverse components are applied over the EC surface. The computational model includes the glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs). We show the distinct effects of atherogenic flow profiles (reversing unidirectional flow and reversing multi-directional flow) on subcellular structures relative to non-atherogenic flow (non-reversing flow). Reversing flow lowers stresses and strains due to viscoelastic effects, and multi-directional flow alters stress on the ADJs perpendicular to the axial flow direction. The simulations predict forces on integrins, ADJ filaments and other substructures in the range that activate mechanotransduction.

Lab on a Chip ◽  
2016 ◽  
Vol 16 (2) ◽  
pp. 360-367 ◽  
Author(s):  
Jiasheng Wang ◽  
Beiyuan Fan ◽  
Yuanchen Wei ◽  
Xingmei Suo ◽  
Yongsheng Ding

A novel microfluidic stretching device capable of providing three-dimensional and axisymmetric strains and inducing inflammatory responses of cells.


Author(s):  
A. Gill ◽  
T. W. von Backström ◽  
T. M. Harms

This article describes an experimental investigation of the flow structures occurring in an axial flow compressor during second quadrant operation for reversed rotor rotation in the incompressible flow regime. In second quadrant operation, the flow direction is reversed, but the pressure is lower at the compressor inlet than at the outlet. The compressor thus acts as an axial flow turbine. A three stage axial flow compressor, with a mass flow rate of 2.7 kg/s and a pressure ratio of 1.022 was investigated. The design rotor tip Mach number is 0.2. Three operational points within the second quadrant were investigated, at flow coefficients of −0.482, −0.553 and −0.843. A five hole conical probe and a 50 micron diameter inclined hot film anemometer were used in this investigation. Radial traverses downstream of rotor rows and a time-dependent area traverse downstream of the first stage stator were performed. Three-dimensional time-dependent numerical Navier-Stokes solutions using the non-linear harmonic approximation for single blade passages in each blade row for each of the cases are compared with experimental work. The compressor has already been show to be capable of attaining relatively high turbine efficiency (76%) when operating in this mode. Examination of the flow field shows that little to no flow separation occurs on the rotor or stator blades. The wakes of all blades are found to be thin and sharp, and the area between wakes is large and approximately uniform. Numerical results agree relatively well with experimental results.


2019 ◽  
Author(s):  
Ioannis Xanthis ◽  
Celine Souilhol ◽  
Jovana Serbanovic-Canic ◽  
Hannah Roddie ◽  
Antreas C. Kalli ◽  
...  

ABSTRACTThe ability of endothelial cells (EC) to sense blood flow direction is a critical determinant of vascular health and disease. Unidirectional flow induces EC alignment and vascular homeostasis, whereas bidirectional flow has pathophysiological effects. EC express several mechanoreceptors that can respond to fluid flow (shear stress) but the mechanism for sensing the direction of shearing force is poorly understood. We observed using in vitro flow systems and magnetic tweezers that β1 integrin is a key sensor of force direction because it is activated by unidirectional but not bidirectional shearing forces. Consistently, β1 integrin was essential for Ca2+ signalling and cell alignment in response to unidirectional but not bidirectional shear stress. β1 integrin activation by unidirectional force was amplified in EC that were pre-sheared in the same direction, indicating that alignment and β1 integrin activity has a feedforward interaction which is a hallmark of system stability. En face staining and EC-specific genetic deletion studies of the murine aorta revealed that β1 integrin is activated and is essential for EC alignment at sites of unidirectional flow but is not activated at sites of bidirectional flow. In summary, β1 integrin sensing of unidirectional force is a key mechanism for decoding blood flow mechanics to promote vascular homeostasis.SUMMARY STATEMENTWe demonstrate using flow systems, magnetic tweezers and knockout mice that β1 integrin is a sensor of shear stress direction in endothelial cells. β1 integrin is activated by unidirectional hemodynamic shear force leading to calcium signalling and cell alignment, but it is not activated by bidirectional force.


2017 ◽  
Vol 68 (6) ◽  
pp. 1341-1344
Author(s):  
Grigore Berea ◽  
Gheorghe Gh. Balan ◽  
Vasile Sandru ◽  
Paul Dan Sirbu

Complex interactions between stem cells, vascular cells and fibroblasts represent the substrate of building microenvironment-embedded 3D structures that can be grafted or added to bone substitute scaffolds in tissue engineering or clinical bone repair. Human Adipose-derived Stem Cells (hASCs), human umbilical vein endothelial cells (HUVECs) and normal dermal human fibroblasts (NDHF) can be mixed together in three dimensional scaffold free constructs and their behaviour will emphasize their potential use as seeding points in bone tissue engineering. Various combinations of the aforementioned cell lines were compared to single cell line culture in terms of size, viability and cell proliferation. At 5 weeks, viability dropped for single cell line spheroids while addition of NDHF to hASC maintained the viability at the same level at 5 weeks Fibroblasts addition to the 3D construct of stem cells and endothelial cells improves viability and reduces proliferation as a marker of cell differentiation toward osteogenic line.


2019 ◽  
Vol 97 ◽  
pp. 272-280 ◽  
Author(s):  
Punn Augsornworawat ◽  
Leonardo Velazco-Cruz ◽  
Jiwon Song ◽  
Jeffrey R. Millman

2021 ◽  
Vol 22 (5) ◽  
pp. 2381
Author(s):  
Hui-Yung Song ◽  
Yi-Ping Yang ◽  
Yueh Chien ◽  
Wei-Yi Lai ◽  
Yi-Ying Lin ◽  
...  

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.


2000 ◽  
Vol 411 ◽  
pp. 1-38 ◽  
Author(s):  
C. ROSS ETHIER ◽  
SUJATA PRAKASH ◽  
DAVID A. STEINMAN ◽  
RICHARD L. LEASK ◽  
GREGORY G. COUCH ◽  
...  

Numerical and experimental techniques were used to study the physics of flow separation for steady internal flow in a 45° junction geometry, such as that observed between two pipes or between the downstream end of a bypass graft and an artery. The three-dimensional Navier–Stokes equations were solved using a validated finite element code, and complementary experiments were performed using the photochromic dye tracer technique. Inlet Reynolds numbers in the range 250 to 1650 were considered. An adaptive mesh refinement approach was adopted to ensure grid-independent solutions. Good agreement was observed between the numerical results and the experimentally measured velocity fields; however, the wall shear stress agreement was less satisfactory. Just distal to the ‘toe’ of the junction, axial flow separation was observed for all Reynolds numbers greater than 250. Further downstream (approximately 1.3 diameters from the toe), the axial flow again separated for Re [ges ] 450. The location and structure of axial flow separation in this geometry is controlled by secondary flows, which at sufficiently high Re create free stagnation points on the model symmetry plane. In fact, separation in this flow is best explained by a secondary flow boundary layer collision model, analogous to that proposed for flow in the entry region of a curved tube. Novel features of this flow include axial flow separation at modest Re (as compared to flow in a curved tube, where separation occurs only at much higher Re), and the existence and interaction of two distinct three-dimensional separation zones.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Zhengzhi Wang ◽  
Chunling Zhu

In view of the rotor icing problems, the influence of centrifugal force on rotor blade icing is investigated. A numerical simulation method of three-dimensional rotor blade icing is presented. Body-fitted grids around the rotor blade are generated using overlapping grid technology and rotor flow field characteristics are obtained by solving N-S equations. According to Eulerian two-phase flow, the droplet trajectories are calculated and droplet impingement characteristics are obtained. The mass and energy conservation equations of ice accretion model are established and a new calculation method of runback water mass based on shear stress and centrifugal force is proposed to simulate water flow and ice shape. The calculation results are compared with available experimental results in order to verify the correctness of the numerical simulation method. The influence of centrifugal force on rotor icing is calculated. The results show that the flow direction and distribution of liquid water on rotor surfaces change under the action of centrifugal force, which lead to the increasing of icing at the stagnation point and the decreasing of icing on both frozen limitations.


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