scholarly journals Lymphatic endothelial cell calcium pulses are sensitive to spatial gradients in wall shear stress

2019 ◽  
Vol 30 (7) ◽  
pp. 923-931
Author(s):  
Vinay N. Surya ◽  
Eleftheria Michalaki ◽  
Gerald G. Fuller ◽  
Alexander R. Dunn

Cytosolic calcium (Ca2+) is a ubiquitous second messenger that influences numerous aspects of cellular function. In many cell types, cytosolic Ca2+ concentrations are characterized by periodic pulses, whose dynamics can influence downstream signal transduction. Here, we examine the general question of how cells use Ca2+ pulses to encode input stimuli in the context of the response of lymphatic endothelial cells (LECs) to fluid flow. Previous work shows that fluid flow regulates Ca2+ dynamics in LECs and that Ca2+-dependent signaling plays a key role in regulating lymphatic valve formation during embryonic development. However, how fluid flow might influence the Ca2+ pulse dynamics of individual LECs has remained, to our knowledge, little explored. We used live-cell imaging to characterize Ca2+ pulse dynamics in LECs exposed to fluid flow in an in vitro flow device that generates spatial gradients in wall shear stress (WSS), such as are found at sites of valve formation. We found that the frequency of Ca2+ pulses was sensitive to the magnitude of WSS, while the duration of individual Ca2+ pulses increased in the presence of spatial gradients in WSS. These observations provide an example of how cells can separately modulate Ca2+ pulse frequency and duration to encode distinct forms of information, a phenomenon that could extend to other cell types.

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask

Endothelial cells are known to respond to hemodynamic forces. Their phenotype has been suggested to differ between atheroprone and atheroprotective regions of the vasculature, which are characterized by the local hemodynamic environment. Once an atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress. Endothelial cell response to wall shear stress may be linked to the stability of coronary plaques. Unfortunately, in vitro studies of the endothelial cell involvement in plaque stability have been limited by unrealistic and simplified geometries, which cannot reproduce accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt to better replicate the spatial wall shear stress gradient patterns in an atherosclerotic region, a three dimensional asymmetric stenosis model was created. Human abdominal aortic endothelial cells were exposed to steady flow (Re=50, 100, and 200 and τ=4.5 dyn/cm2, 9 dyn/cm2, and 18 dyn/cm2) in idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local morphological changes that occur due to magnitude, duration, and spatial gradients were quantified to identify differences in cell response. In the one dimensional flow regions, where flow is fully developed and uniform wall shear stress is observed, cells aligned in flow direction and had a spindlelike shape when compared with static controls. Morphological changes were progressive and a function of time and magnitude in these regions. Cells were more randomly oriented and had a more cobblestone shape in regions of spatial wall shear stress gradients. These regions were present, both proximal and distal, at the stenosis and on the wall opposite to the stenosis. The response of endothelial cells to spatial wall shear stress gradients both in regions of acceleration and deceleration and without flow recirculation has not been previously reported. This study shows the dependence of endothelial cell morphology on spatial wall shear stress gradients and demonstrates that care must be taken to account for altered phenotype due to geometric features. These results may help explain plaque stability, as cells in shoulder regions near an atherosclerotic plaque had a cobblestone morphology indicating that they may be more permeable to subendothelial transport and express prothrombotic factors, which would increase the risk of atherothrombosis.


2021 ◽  
Author(s):  
Amira Husni Talib ◽  
Ilyani Abdullah ◽  
Nik Nabilah Nik Mohd Naser

2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.


Author(s):  
Han-Sheng Chuang ◽  
Steven T. Wereley

Conventional single pixel evaluation (SPE) significantly improves the spatial resolution of PIV measurements to the physical limit of a CCD camera based on the forward difference interrogation (FDI). This paper further enhances the computational algorithm to second-order accuracy by simply modifying the numerical scheme with the central difference interrogation (CDI). The proposed central difference scheme basically superposes the forward-time and the backward-time correlation domains, thus resulting in reduced bias error as well as rapid background noise elimination. An assessment of the CDI SPE algorithm regarding the measurement errors was achieved via numerous synthetic images subject to a four-roll mill flow. In addition, preliminary wall shear stress (WSS) measurements regarding different algorithms are also evaluated with an analytical turbulent boundary flow. CDI scheme showed a 0.32% error deviated from the analytical solution and improved the same error in FFT-based correlation correlation (FFT-CC) by 32.35%. To demonstrate the performance in practice, in-vitro measurements were implemented in a serpentine microchannel made of polydimethyl siloxane (PDMS) for both CDI SPE and spatial cross-correlation. A series of steady-state flow images at five specified regions of interest were acquired using micro-PIV system. Final comparisons of the WSS regarding the Pearson correlation coefficient, R2, between the numerical schemes and the simulations showed that an overall result was improved by CDI SPE due to the fine resolution and the enhanced accuracy.


Biomechanisms ◽  
1992 ◽  
Vol 11 (0) ◽  
pp. 99-109 ◽  
Author(s):  
Takashi HIROSE ◽  
Akio TANABE ◽  
Kazuo TANISHITA

2019 ◽  
Vol 131 (2) ◽  
pp. 442-452 ◽  
Author(s):  
Alexandra Lauric ◽  
James E. Hippelheuser ◽  
Adel M. Malek

OBJECTIVEEndothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide branching angles with aneurysm presence, the authors evaluated the effect of bifurcation geometry on local apical hemodynamics.METHODSComputational fluid dynamics simulations were performed on parametric bifurcation models with increasing angles having: 1) symmetrical geometry (bifurcation angle 60°–180°), 2) asymmetrical geometry (daughter angles 30°/60° and 30°/90°), and 3) curved parent vessel (bifurcation angles 60°–120°), all at baseline and double flow rate. Time-dependent and time-averaged apical WSS and WSSG were analyzed. Results were validated on patient-derived models.RESULTSNarrow symmetrical bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles ≥ 85°. Asymmetrical bifurcations develop positive WSSG on the more obtuse daughter branch. A curved parent vessel leads to positive apical WSSG on the side corresponding to the outer curve. All simulations revealed wider apical area coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation angle and higher flow rate. Flow rate did not affect the angle threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex, in a dynamic fashion and in an angle-dependent manner.CONCLUSIONSApical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The development of aneurysmogenic positive WSSG as a function of angular geometry provides a mechanotransductive link for the association of wide bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the associated aneurysmal degeneration.


Author(s):  
Risa Robinson ◽  
Lynn Fuller ◽  
Harvey Palmer ◽  
Mary Frame

Blood flow regulation in the microvascular network has been investigated by means of computational fluid dynamics, in vivo particle tracking and microchannel models. It is evident from these studies that shear stress along the wall is a key factor in the communication network that results in blood flow modification, yet current methods for shear stress determination are acknowledged to be imprecise. Micromachining technology allows for the development of implantable shear stress sensors that will enable us to monitor wall shear stress at multiple locations in arteriole bifurcations. In this study, a microchannel was employed as an in vitro model of a microvessel. Thermal shear stress sensors were used to mimic the endothelial cells that line the vessel wall. A three dimensional computational model was created to simulate the system’s thermal response to the constant temperature control circuit and related wall shear stress. The model geometry included a silicon wafer section with all the fabrication layers — silicon dioxide, poly silicon resistor, silicon nitride — and a microchannel with cross section 17 μm × 17 μm. This computational technique was used to optimize the dimensions of the system for a 0.01 Reynolds number flow at room temperature in order to reduce the amount of heat lost to the substrate and to predict and maximize the signal response. Results of the design optimization are presented and the fabrication process discussed.


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