Development of Microfluidic Chips to Study the Effects of Shear Stress on Cell Functions

2010 ◽  
Author(s):  
Jianbin Wang ◽  
Jinseok Heo ◽  
Susan Z. Hua
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Cellular Systems ◽  
Shear Stresses ◽  
Microfluidic Chips ◽  
Fluid Shear ◽  
Cell Functions ◽  
Culture Cells ◽  
Wide Range ◽  
On Chip

Fluid shear stress has profound effect on many cell functions, including proliferation, migration, transport, and gene expression. Cellular systems such as endothelial cells in heart artery and epithelial cells in kidney tubule are constantly subject to fluid flow. We have developed a series of microfluidic chips that generate a wide range and modes of shear stresses within a perfusion chamber, enabling us to culture cells on chip and examine the effects of shear stress on cell growth and cell functions.

The Dynamic Response of Vascular Endothelial Cells to Fluid Shear Stress

1981 ◽  
Vol 103 (3) ◽  
pp. 177-185 ◽  
Author(s):  
C. F. Dewey ◽  
S. R. Bussolari ◽  
M. A. Gimbrone ◽  
P. F. Davies
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Dynamic Response ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cells ◽  
Shear Stresses ◽  
Vascular Endothelial ◽  
Fluid Shear ◽  
Cell Functions

We have developed an in-vitro system for studying the dynamic response of vascular endothelial cells to controlled levels of fluid shear stress. Cultured monolayers of bovine aortic endothelial cells are placed in a cone-plate apparatus that produces a uniform fluid shear stress on replicate samples. Subconfluent endothelial cultures continuously exposed to 1–5 dynes/cm2 shear proliferate at a rate comparable to that of static cultures and reach the same saturation density (≃ 1.0–1.5 × 105 cells/cm2). When exposed to a laminar shear stress of 5–10 dynes/cm2, confluent monolayers undergo a time-dependent change in cell shape from polygonal to ellipsoidal and become uniformly oriented with flow. Regeneration of linear “wounds” in confluent monolayer appears to be influenced by the direction of the applied force. Preliminary studies indicate that certain endothelial cell functions, including fluid endocytosis, cytoskeletal assembly and nonthrombogenic surface properties, also are sensitive to shear stress. These observations suggest that fluid mechanical forces can directly influence endothelial cell structure and function. Modulation of endothelial behavior by fluid shear stresses may be relevant to normal vessel wall physiology, as well as the pathogenesis of vascular diseases, such as atherosclerosis.

Effects of Fluid Shear Stress on Endothelial Cell Invasion Into Three-Dimensional Matrices

2007 ◽  
Author(s):  
Hojin Kang ◽  
Kayla J. Bayless ◽  
Roland Kaunas
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Invasion ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Shear Stresses ◽  
Collagen Gels ◽  
Fluid Shear

We have previously developed a cell culture model to study the effects of angiogenic factors, such as sphingosine-1-phosphate (S1P), on the invasion of endothelial cells into the underlying extracellular matrix. In addition to biochemical stimuli, vascular endothelial cells are subjected to fluid shear stress due to blood flow. The present study is aimed at determining the effects of fluid shear stress on endothelial cell invasion into collagen gels. A device was constructed to apply well-defined fluid shear stresses to confluent human umbilical vein endothelial cells (HUVECs) seeded on collagen gels. Fluid shear stress induced significant increases in cell invasion with a maximal induction at ∼5 dyn/cm2. These results provide evidence that fluid shear stress is a significant stimulus for endothelial cell invasion and may play a role in regulating angiogenesis.

A systematic investigation of the effect of the fluid shear stress on Caco-2 cells towards the optimization of epithelial organ-on-chip models

Biomaterials ◽  
2019 ◽  
Vol 225 ◽  
pp. 119521 ◽  
Author(s):  
Ludivine C. Delon ◽  
Zhaobin Guo ◽  
Anna Oszmiana ◽  
Chia-Chi Chien ◽  
Rachel Gibson ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Systematic Investigation ◽  
Fluid Shear ◽  
On Chip

The Fluid Shear Stress Distribution on the Membrane of Leukocytes in the Microcirculation

2003 ◽  
Vol 125 (5) ◽  
pp. 628-638 ◽  
Author(s):  
Masako Sugihara-Seki ◽  
Geert W. Schmid-Scho¨nbein
Keyword(s):  
Shear Stress ◽  
Stress Distribution ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Shear Stress Distribution ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Stress Gradients ◽  
Freely Suspended ◽  
Microvessel Wall

Recent in-vivo and in-vitro evidence indicates that fluid shear stress on the membrane of leukocytes has a powerful control over several aspects of their cell function. This evidence raises a question about the magnitude of the fluid shear stress on leukocytes in the circulation. The flow of plasma on the surface of a leukocyte at a very low Reynolds number is governed by the Stokes equation for the motion of a Newtonian fluid. We numerically estimated the distribution of fluid shear stress on a leukocyte membrane in a microvessel for the cases when the leukocyte is freely suspended, as well as rolling along or attached to a microvessel wall. The results indicate that the fluid shear stress distribution on the leukocyte membrane is nonuniform with a sharp increase when the leukocyte makes membrane attachment to the microvessel wall. In a microvessel (10 μm diameter), the fluid shear stress on the membrane of a freely suspended leukocyte (8 μm diameter) is estimated to be several times larger than the wall shear stress exerted by the undisturbed Poiseuille flow, and increases on an adherent leukocyte up to ten times. High temporal stress gradients are present in freely suspended leukocytes in shear flow due to cell rotation, which are proportional to the local shear rate. In comparison, the temporal stress gradients are reduced on the membrane of leukocytes that are rolling or firmly adhered to the endothelium. High temporal gradients of shear stress are also present on the endothelial wall. At a plasma viscosity of 1 cPoise, the peak shear stresses for suspended and adherent leukocytes are of the order of 10 dyn/cm2 and 100 dyn/cm2, respectively.

scholarly journals Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1366-1374 ◽  
Author(s):  
JL Moake ◽  
NA Turner ◽  
NA Stathopoulos ◽  
L Nolasco ◽  
JD Hellums
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Fluid Shear Stress ◽  
Thrombus Formation ◽  
Adenosine Diphosphate ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Von Willebrand ◽  
Induced Aggregation

Abstract Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large von Willebrand factor (vWF) multimers in the suspending fluid exogenous to the platelets mediates aggregation. Adenosine diphosphate (ADP) is also required and, in these experiments, was released from the platelets subjected to shear stress. At 120 dyne/cm2, the release of endogenous platelet vWF multimers can substitute for exogenous large or unusually large vWF forms in mediating aggregation. Endogenous released platelet vWF forms, as well as exogenous large or unusually large vWF multimers, must bind to both glycoproteins Ib and the IIb/IIIa complex to produce aggregation. Shear- induced aggregation is the result of shear stress alteration of platelet surfaces, rather than of shear effects on vWF multimers. It is mediated by either large plasma-type vWF multimers, endogenous released platelet vWF forms, or unusually large vWF multimers derived from endothelial cells, requires ADP, and is not inhibited significantly by aspirin. This type of aggregation may be important in platelet thrombus formation within narrowed arterial vessels, and may explain the limited therapeutic utility of aspirin in arterial thrombosis.

Experimental Technique of Measuring Dynamic Fluid Shear Stress on the Aortic Surface of the Aortic Valve Leaflet

2011 ◽  
Vol 133 (6) ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Steady Flow ◽  
Fluid Shear Stress ◽  
Shear Stresses ◽  
Straight Tube ◽  
Valve Leaflet ◽  
Fluid Shear ◽  
Valve Model

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5dyn/cm2) but elevated to its peak during mid to late systole at about 18–20 dyn/cm2. Low magnitude shear stress (<5dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.

scholarly journals The influence of temperature on red cell deformability

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 611-624 ◽  
Author(s):  
JR Williamson ◽  
MO Shanahan ◽  
RM Hochmuth
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Red Cells ◽  
Shear Stresses ◽  
Red Cell ◽  
Fluid Shear ◽  
Rotating Disc ◽  
Red Cell Deformability ◽  
Influence Of Temperature ◽  
Influence Of Temperature On

Abstract This study was undertaken to examine the influence of temperature on physical properties of red cell membranes. Red cells adhering to cover slips were subjected to fluid shear stress in a rotating disc apparatus for 1 min or for 10 min at temperatures ranging from 2 degrees to 50 degress C. They were fixed while subject to shear stress by addition of glutaraldehyde and then processed for examination and photography by reflected-light microscopy. Cell dimensions were obtained with a computerized planimeter. At shear stresses under 2 dynes/sq cm, cells changed shape from biconcave discs to tear drops, the dimensions of which were influenced very little by temperature or duration of shear stress. Above 2 dynes/sq cm, filamentous processes or “tethers” developed at attachment points of cells to cover slips. Tether length and the percentage of cells possessing tethers increased markedly with increasing temperature and duration of shear stress. At approximately 48 degrees C, a dramatic change occurred over a narrow temperature range such that cells were markedly elongated and irregularly deformed by a shear stress of 1 dyne/sq cm or less. These observations demonstrate that elongation of human red cells subjected to fluid shear stress in a rotating disc system is markedly influenced by temperature as well as by magnitude and duration of shear stress. They also indicate that significant increases in red cell membrane fluidity occur between 2 degrees and 24 degrees-37 degrees C and again between 48 degrees and 50 degrees C.

Design and analysis of microfluidic kidney-on-chip model: fluid shear stress based study with temperature effect

2018 ◽  
Vol 25 (7) ◽  
pp. 2553-2560 ◽  
Author(s):  
Jasti Sateesh ◽  
Koushik Guha ◽  
Arindam Dutta ◽  
Pratim Sengupta ◽  
K. Srinivasa Rao
Keyword(s):  
Shear Stress ◽  
Temperature Effect ◽  
Fluid Shear Stress ◽  
Fluid Shear ◽  
Model Fluid ◽  
On Chip

An Apparatus to Study the Response of Cultured Endothelium to Shear Stress

1986 ◽  
Vol 108 (4) ◽  
pp. 332-337 ◽  
Author(s):  
R. F. Viggers ◽  
A. R. Wechezak ◽  
L. R. Sauvage
Keyword(s):  
Finite Element ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Laminar Flow ◽  
Fluid Shear Stress ◽  
Shear Stresses ◽  
Parallel Plates ◽  
Dimensional Flow ◽  
Wide Range ◽  
Wall Shear

An apparatus which has been developed to study the response of cultured endothelial cells to a wide range of shear stress levels is described. Controlled laminar flow through a rectangular tube was used to generate fluid shear stress over a cell-lined coverslip comprising part of one wall of the tube. A finite element method was used to calculate shear stresses corresponding to cell position on the coverslip. Validity of the finite element analysis was demonstrated first by its ability to generate correctly velocity profiles and wall shear stresses for laminar flow in the entrance region between infinitely wide parallel plates (two-dimensional flow). The computer analysis also correctly predicted values for pressure difference between two points in the test region of the apparatus for the range of flow rates used in these experiments. These predictions thus supported the use of such an analysis for three-dimensional flow. This apparatus has been used in a series of experiments to confirm its utility for testing applications. In these studies, endothelial cells were exposed to shear stresses of 60 and 128 dynes/cm2. After 12 hr at 60 dynes/cm2, cells became aligned with their longitudinal axes parallel to the direction of flow. In contrast, cells exposed to 128 dynes/cm2 required 36 hr to achieve a similar reorientation. Interestingly, after 6 hr at 128 dynes/cm2, specimens passed through an intermediate phase in which cells were aligned perpendicular to flow direction. Because of its ease and use and the provided documentation of wall shear stress, this flow chamber should prove to be a valuable tool in endothelial research related to atherosclerosis.

scholarly journals The influence of temperature on red cell deformability

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 611-624 ◽  
Author(s):  
JR Williamson ◽  
MO Shanahan ◽  
RM Hochmuth
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Red Cells ◽  
Shear Stresses ◽  
Red Cell ◽  
Fluid Shear ◽  
Rotating Disc ◽  
Red Cell Deformability ◽  
Influence Of Temperature ◽  
Influence Of Temperature On

This study was undertaken to examine the influence of temperature on physical properties of red cell membranes. Red cells adhering to cover slips were subjected to fluid shear stress in a rotating disc apparatus for 1 min or for 10 min at temperatures ranging from 2 degrees to 50 degress C. They were fixed while subject to shear stress by addition of glutaraldehyde and then processed for examination and photography by reflected-light microscopy. Cell dimensions were obtained with a computerized planimeter. At shear stresses under 2 dynes/sq cm, cells changed shape from biconcave discs to tear drops, the dimensions of which were influenced very little by temperature or duration of shear stress. Above 2 dynes/sq cm, filamentous processes or “tethers” developed at attachment points of cells to cover slips. Tether length and the percentage of cells possessing tethers increased markedly with increasing temperature and duration of shear stress. At approximately 48 degrees C, a dramatic change occurred over a narrow temperature range such that cells were markedly elongated and irregularly deformed by a shear stress of 1 dyne/sq cm or less. These observations demonstrate that elongation of human red cells subjected to fluid shear stress in a rotating disc system is markedly influenced by temperature as well as by magnitude and duration of shear stress. They also indicate that significant increases in red cell membrane fluidity occur between 2 degrees and 24 degrees-37 degrees C and again between 48 degrees and 50 degrees C.

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