Biofunctionalization via flow shear stress resistant adhesive polysaccharide, hyaluronic acid-catechol, for enhanced in vitro endothelialization

Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 but not EP4, and increased synthesis and secretion of PGE2, which were effectively blocked by indomethacin. Next, we developed a special flow chamber for applying FFSS to isolated glomeruli to determine its effect on an intact glomerular filtration barrier by measuring change in albumin permeability ( Palb) in vitro. FFSS caused an increase in Palb that was blocked by indomethacin ( P < 0.001). Finally, we show that unilateral nephrectomy in sv129 mice resulted in glomerular hypertrophy ( P = 0.006), increased glomerular expression of COX-2 ( P < 0.001) and EP2 ( P = 0.039), and increased urinary albumin excretion ( P = 0.001). Activation of the COX-2-PGE2-EP2 axis appears to be a specific response to FFSS in podocytes and provides a mechanistic basis for alteration in podocyte structure and the glomerular filtration barrier, leading to albuminuria in hyperfiltration-mediated kidney injury. The COX-2-PGE2-EP2 axis is a potential target for developing specific interventions to ameliorate the effects of hyperfiltration-mediated kidney injury in the progression of chronic kidney disease.

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The Effect of Fluid Flow Shear Stress and Substrate Stiffness on Yes-Associated Protein (YAP) Activity and Osteogenesis in Murine Osteosarcoma Cells

Cancers ◽

10.3390/cancers13133128 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3128

Author(s):

Thomas R. Coughlin ◽

Ali Sana ◽

Kevin Voss ◽

Abhilash Gadi ◽

Upal Basu-Roy ◽

...

Keyword(s):

Shear Stress ◽

Fluid Flow ◽

Bone Cells ◽

Bone Cancer ◽

Substrate Stiffness ◽

Flow Shear ◽

Fluid Movement ◽

Flow Shear Stress ◽

Fluid Flow Shear Stress ◽

New Treatments

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in the osteoblast lineage. We silenced Sox2 (which regulates YAP) and tested the effect of fluid flow shear stress (FFSS) and substrate stiffness on YAP expression/activity—which was significantly reduced by loss of Sox2, but that effect was reversed by FFSS but not by substrate stiffness. Osteogenic gene expression was also reduced in the absence of Sox2 but again this was reversed by FFSS and remained largely unaffected by substrate stiffness. Thus we described the effect of two distinct stimuli on the mechanosensory and osteogenic profiles of OS cells. Taken together, these data suggest that modulation of fluid movement through, or stiffness levels within, OS tumors could represent a novel consideration in the development of new treatments to prevent their progression.

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Temporal gradient in shear-induced signaling pathway: involvement of MAP kinase, c-fos, and connexin43

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.278.5.h1598 ◽

2000 ◽

Vol 278 (5) ◽

pp. H1598-H1605 ◽

Cited By ~ 68

Author(s):

Xuping Bao ◽

Craig B. Clark ◽

John A. Frangos

Keyword(s):

Shear Stress ◽

Mrna Expression ◽

Signaling Pathway ◽

Steady Shear ◽

Flow Shear ◽

Temporal Gradient ◽

Step Flow ◽

Shear Component ◽

Flow Shear Stress ◽

Impulse Flow

The effect of a temporal gradient in shear and steady shear on the activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/ERK2), c- fos, and connexin43 (Cx43) in human endothelial cells was investigated. Three laminar flow profiles (16 dyn/cm2), including impulse flow (shear stress abruptly applied for 3 s), ramp flow (shear stress smoothly transitioned at flow onset), and step flow (shear stress abruptly applied at flow onset) were utilized. Relative to static controls, impulse flow stimulated the phosphorylation of ERK1/ERK2 8.5- to 7.5-fold, respectively at 10 min, as well as the mRNA expression of c- fos 51-fold at 30 min, and Cx43 8-fold at 90 min. These high levels of mRNA expression were sustained for at least 4 h. In contrast, ramp flow was unable to significantly induce gene expression and even inhibited the activation of ERK1/ERK2. Step flow, which contains both a sharp temporal gradient in shear stress and a steady shear component, elicited only moderate and transient responses, indicating the distinct role of these fluid shear stimuli in endothelial signal transduction. The specific inhibitor of mitogen-activated protein kinase kinase PD-98059 inhibited impulse flow-induced c -fos and Cx43 mRNA expression. Thus these findings implicate the involvement of ERK1/ERK2, c -fos, and Cx43 in the signaling pathway induced by the temporal gradient in shear.

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Microfluidic models of physiological or pathological flow shear stress for cell biology, disease modeling and drug development

TrAC Trends in Analytical Chemistry ◽

10.1016/j.trac.2019.06.023 ◽

2019 ◽

Vol 117 ◽

pp. 186-199 ◽

Cited By ~ 7

Author(s):

Huaying Chen ◽

Zhihang Yu ◽

Siwei Bai ◽

Huaxiu Lu ◽

Dong Xu ◽

...

Keyword(s):

Shear Stress ◽

Drug Development ◽

Cell Biology ◽

Disease Modeling ◽

Flow Shear ◽

Flow Shear Stress

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From soil aggregates to riverine flocs: a laboratory experiment assessing the respective effects of soil type and flow shear stress on particles characteristics

Hydrological Processes ◽

10.1002/hyp.9929 ◽

2013 ◽

Vol 28 (13) ◽

pp. 4141-4155 ◽

Cited By ~ 10

Author(s):

T. Grangeon ◽

I. G. Droppo ◽

C. Legout ◽

M. Esteves

Keyword(s):

Shear Stress ◽

Laboratory Experiment ◽

Soil Type ◽

Soil Aggregates ◽

Flow Shear ◽

Flow Shear Stress

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Advanced human carotid plaque progression correlates positively with flow shear stress using follow-up scan data: An in vivo MRI multi-patient 3D FSI study

Journal of Biomechanics ◽

10.1016/j.jbiomech.2010.05.018 ◽

2010 ◽

Vol 43 (13) ◽

pp. 2530-2538 ◽

Cited By ~ 44

Author(s):

Chun Yang ◽

Gador Canton ◽

Chun Yuan ◽

Marina Ferguson ◽

Thomas S. Hatsukami ◽

...

Keyword(s):

Shear Stress ◽

Carotid Plaque ◽

Plaque Progression ◽

Flow Shear ◽

Flow Shear Stress ◽

Scan Data ◽

Human Carotid

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The Influence of Temperature and Humidity on the ABS Contaminations

2014 Conference on Information Storage and Processing Systems ◽

10.1115/isps2014-6981 ◽

2014 ◽

Cited By ~ 2

Author(s):

Fuhao Cui ◽

Jinhong Hu ◽

Yue Peng ◽

Hui Li ◽

Shengnan Shen ◽

...

Keyword(s):

Shear Stress ◽

Flow Pattern ◽

Air Flow ◽

Disk Drive ◽

Flying Height ◽

Flow Shear ◽

Slip Boundary ◽

Temperature And Humidity ◽

Flow Shear Stress ◽

The Impact

In order to increase the areal recording density of hard disk drive beyond 1 Tb/in2, the flying height has to be reduced to several nanometers. At such a low flying height, particles and lube contaminations, which could lead to a transient vibration and flying height modulation in a hard disk drive, are becoming more and more serious. In this work, it studies the influence of temperature and humidity on the air flow pattern, velocity and shear stress distribution on the air bearing surface (ABS) of slider using a self-developed simulator. It first solves the generalized steady state Reynolds equation with slip boundary conditions. Then it solves the reduced Navier-Stokes (N-S) equation with slip boundary conditions to get the air velocity distribution, i.e., identify the air flow pattern on the ABS. The stagnation lines and areas of air flow are calculated to judge the contamination area. On the other hand, it calculates the air shear stress distribution on the ABS since the air shear stress is the main driving force for the lubricant and particles migration and contaminations. After that, the impact of the temperature and humidity on the air flow pattern is analyzed by applying the Sutherland equation and mixed gas viscosity calculation equation. The simulation results indicate that the impact of temperature and humidity on the air flow pattern is un-conspicuous. However, the peak velocity of the air flow, which contains no vapor, reduces almost 10%, and the peak air flow shear stress increases less than 1.5%, with the increase of operational temperature from 298.15 K to 343.15 K. In addition, the peak velocity of the air flow increasing almost 4%, and the peak air flow shear stress keeps almost same, with the increase of the operational mole fraction of vapor from 5% to 15%.

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A New Hypothesis for Human Atherosclerotic Plaque Progression Based on Serial In Vivo MRI and Computational Modeling Method

ASME 2007 Summer Bioengineering Conference ◽

10.1115/sbc2007-175504 ◽

2007 ◽

Author(s):

Sayan Mondal ◽

Chun Yang ◽

Joseph D. Petruccelli ◽

Chun Yuan ◽

Fei Liu ◽

...

Keyword(s):

Shear Stress ◽

Wall Thickness ◽

Computational Models ◽

Ex Vivo ◽

Maximum Principal Stress ◽

Magnetic Resonance Images ◽

Shear Stresses ◽

Flow Shear ◽

Flow Shear Stress

It has been well-accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses. However, this shear stress mechanism cannot fully explain why advanced plaques continue to grow under elevated flow shear stress conditions. Our previous investigations using 3D computational models with fluid-structure interactions (FSI) based on in vivo/ex vivo magnetic resonance images (MRI) of human carotid atherosclerotic plaques indicated that there is a negative correlation between advanced plaque wall thickness and structural maximum principal stress (Stress-P1) in the plaque and a positive correlation between plaque wall thickness and flow shear stress [3].

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