scholarly journals Microfluidic chip grafted with integrin tension sensors for evaluating the effects of flowing shear stress and ROCK inhibitor on platelets

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Subin Mao ◽  
Anwesha Sarkar ◽  
Yongliang Wang ◽  
Chao Song ◽  
Dana Nicole LeVine ◽  
...  

Integrins are key players in platelet adhesion and aggregation. Integrin molecular tensions, the forces transmitted by integrin molecules, are regulated by both mechanical and biochemical cues, and the outside-in and...

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Cui He ◽  
Lihua Yu ◽  
Wenran Dan ◽  
Surong Deng ◽  
Haidong Ma ◽  
...  

This study aimed to develop a simple microfluidic chip analysis technology to study the inhibitory effect of protocatechuic acid on shear-induced platelet aggregation. The microfluidic chip designed in this study simulates 80% fixed narrow microchannels. This microchannel narrow model uses the finite element analysis module of the three-dimensional modeling software solidwork to analyze fluid dynamic behavior. Blood treated with protocatechuic acid at 1, 2, 4, 8, or 16 µg/mL was passed through the microchannel stenosis model at a shear rate of 10,000 s−1. The platelet adhesion and aggregation behaviors were then measured using fluorescence microscopy and observed in real time. Simultaneously, the antiplatelet aggregation effect of protocatechuic acid was analyzed using thromboelastography and photoelectric turbidimetry. The designed stenosis model of the microfluidic chip can produce a gradient of fluid shear rate, and the gradient of fluid shear rate can induce platelet aggregation. Under this model, the degree of platelet adhesion and aggregation increased as the shear rate increased. In the experimental concentration range of 0–8 µmol/mL, protocatechuic acid exerted a concentration-dependent inhibition of platelet aggregation. In contrast, thromboelastography and photoelectric turbidimetry failed to demonstrate an inhibitory effect. The microfluidic chip analysis technology developed in this study can be used to study the effect of protocatechin in inhibiting platelet aggregation induced by shear rate in vitro. This technology is simple to operate and can be used as a new type of antiplatelet aggregation analysis technology for screening studies of novel potential antiplatelet aggregation drugs.


ASAIO Journal ◽  
2000 ◽  
Vol 46 (6) ◽  
pp. 696-701 ◽  
Author(s):  
Katsuko Sakai Furukawa ◽  
Takashi Ushida ◽  
Hirohito Sugano ◽  
Tamotsu Tamaki ◽  
Norio Ohshima ◽  
...  

2006 ◽  
Vol 26 (3) ◽  
pp. 670-675 ◽  
Author(s):  
Cees Weeterings ◽  
Jelle Adelmeijer ◽  
Timothy Myles ◽  
Philip G. de Groot ◽  
Ton Lisman

2008 ◽  
Vol 99 (01) ◽  
pp. 108-115 ◽  
Author(s):  
Koichiro Yano ◽  
Ken-ichi Tsubota ◽  
Takuji Ishikawa ◽  
Shigeo Wada ◽  
Takami Yamaguchi ◽  
...  

SummaryWe propose a method to analyze platelet adhesion and aggregation computationally, taking into account the distinct properties of two plasma proteins, vonWillebrand factor (vWF) and fibrinogen (Fbg). In this method, the hydrodynamic interactions between platelet particles under simple shear flow were simulated using Stokesian dynamics based on the additivity of velocities. The binding force between particles mediated by vWF and Fbg was modeled using the Voigt model. Two Voigt models with different properties were introduced to consider the distinct behaviors of vWF and Fbg. Our results qualitatively agreed with the general observation of a previous in-vitro experiment, thus demonstrating that the significant development of thrombus formation in height requires not only vWF, but also Fbg. This agreement of simulation and experimental results qualitatively validates our model and suggests that consideration of the distinct roles of vWF and Fbg is essential to investigate the physiological and pathophysiological mechanisms of thrombus formation using a computational approach.


2011 ◽  
Vol 31 (04) ◽  
pp. 275-280 ◽  
Author(s):  
U. Budde ◽  
R. Schneppenheim

SummaryVon Willebrand factor (VWF) is an adhesive, multi-functional huge multimerized protein with multiple domains harboring binding sites for collagen, platelet glycoprotein receptors and coagulation factor VIII (FVIII). The functional domains enable VWF to bind to the injured vessel wall, to recruit platelets to the site of injury by adhesion and aggregation and to bind and protect FVIII, an important cofactor of the coagulation cascade. VWF function in primary haemostasis is located in particular in the arterial and micro-circulation. This environment is exposed to high shear forces with hydrodynamic shear rates ranging over several orders of magnitude from 10–1 to 105 s-1 and requires particular mechanisms to enable platelet adhesion and aggregation under these variable conditions. The respective VWF function is strictly correlating with its multimer size. Lack or reduction of large VWF multimers is seen in patients with von Willebrand disease (VWD) type 2A which correlates with reduction of both VWF:platelet GPIb-binding and VWF:collagen binding and a bleeding phenotype. To prevent unlimited platelet adhesion and aggregation which is the cause of the microangiopathic disorder thrombotic thrombocytopenic purpura (TTP), VWF function is regulated by its specific protease ADAMTS13. Whereas a particular susceptibility of VWF to ADAMTS13 proteolysis is the cause of a frequent VWD type 2A phenotype, lack or dysfunction of ADAMTS13, either acquired by ADAMTS13 antibodies or by inherited ADAMTS13 deficiency (Upshaw-Schulman Syndrome), causes TTP. Therefore VWD and TTP represent the opposite manifestations of VWF related disorders, tightly linked to each other.


2003 ◽  
Vol 68B (1) ◽  
pp. 53-58 ◽  
Author(s):  
Marco Bonifazi ◽  
Anna Maria Aloisi ◽  
Ilaria Ceccarelli ◽  
Stefania Lamponi ◽  
Leda Lodi ◽  
...  

Lab on a Chip ◽  
2009 ◽  
Vol 9 (21) ◽  
pp. 3118 ◽  
Author(s):  
Jianbo Shao ◽  
Lei Wu ◽  
Jianzhang Wu ◽  
Yunhuan Zheng ◽  
Hui Zhao ◽  
...  

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