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Influence of dynamic flow conditions on adsorbed plasma protein corona and surface-induced thrombus generation on antifouling brushes
Biomaterials ( IF 14.0 ) Pub Date : 2018-03-08 , DOI: 10.1016/j.biomaterials.2018.03.009
Kai Yu , Paula Andruschak , Han Hung Yeh , Dana Grecov , Jayachandran N. Kizhakkedathu

The information regarding the nature of protein corona (and its changes) and cell binding on biomaterial surface under dynamic conditions is critical to dissect the mechanism of surface-induced thrombosis. In this manuscript, we investigated the nature of protein corona and blood cell binding in heparinized recalcified human plasma, platelet rich plasma and whole blood on three highly hydrophilic antifouling polymer brushes, (poly(N, N-dimethylacrylamide) (PDMA), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA)) using an in vitro blood loop model at comparable arterial and venous flow, and static conditions. A fluid dynamics model was used initially to better understand the resulting flow patterns in a vertical channel containing the substrates to arrive at the placement of the substrates within the blood loop. The protein binding on the brush modified substrates was determined using ellipsometry, fluorescence microscopy and the nature of the protein corona was investigated using mass spectrometry based proteomics. The flow elevated fouling on brush coated surface from blood. The extent of plasma protein adsorption and platelet adhesion onto PDMA brush was lower than other surfaces in both static and flow conditions. The profiles of adsorbed protein corona showed strong dependence on static or flow condition, and the chemistry of the polymer brushes. Specially, the PDMA brushes under flow conditions was more enriched with coagulation proteins, complement proteins, vitronectin and fibronectin but was less enriched with serum albumin. Apolipoprotein B-100 and complement proteins were the most abundant proteins seen on PMPC and PHPMA surfaces under both flow and static conditions, respectively. Unlike PDMA brush, the flow conditions did not affect the composition of protein corona on PMPC and PHPMA brushes. The nature of the protein corona formed in flow conditions influenced the platelet and red blood cell binding. The dependence of shear stress on platelet adhesion from platelet rich plasma and whole blood highlights the contribution of red blood cells in enhancing platelet adhesion on the surface under high shear condition.



中文翻译:

动态流动条件对防污刷吸附血浆蛋白电晕和表面诱导的血栓生成的影响

有关蛋白质电晕性质(及其变化)和动态条件下生物材料表面细胞结合的信息对于剖析表面血栓形成的机制至关重要。在本手稿中,我们研究了在三种高度亲水的防污聚合物刷((N(N,N-二甲基丙烯酰胺)(PDMA),P( 2-甲基丙烯酰氧基乙基磷酰胆碱)(PMPC)和聚[ N-(2-羟丙基)甲基丙烯酰胺](PHPMA))在体外使用在相当的动脉和静脉血流以及静态条件下的血液循环模型。最初使用流体动力学模型来更好地理解在包含底物的垂直通道中产生的流动模式,以达到将底物放置在血液循环内的目的。使用椭圆偏振光度法,荧光显微镜法确定在刷修饰的底物上的蛋白质结合,并使用基于质谱的蛋白质组学研究蛋白质电晕的性质。流动增加了血液在刷涂表面上的积垢。在静态和流动条件下,血浆蛋白在PDMA刷上的吸附和血小板粘附程度均低于其他表面。吸附的蛋白质电晕的轮廓显示出强烈依赖于静态或流动条件以及聚合物刷的化学性质。特别,在流动条件下,PDMA刷富含凝结蛋白,补体蛋白,玻连蛋白和纤连蛋白,而血清白蛋白则较少。载脂蛋白B-100和补体蛋白分别是在流动和静态条件下在PMPC和PHPMA表面上看到的最丰富的蛋白。与PDMA刷子不同,流动条件不影响PMPC和PHPMA刷子上蛋白质电晕的组成。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。补体蛋白,玻连蛋白和纤连蛋白,但血清白蛋白含量较低。载脂蛋白B-100和补体蛋白分别是在流动和静态条件下在PMPC和PHPMA表面上看到的最丰富的蛋白。与PDMA刷子不同,流动条件不影响PMPC和PHPMA刷子上蛋白质电晕的组成。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。补体蛋白,玻连蛋白和纤连蛋白,但血清白蛋白含量较低。载脂蛋白B-100和补体蛋白分别是在流动和静态条件下在PMPC和PHPMA表面上看到的最丰富的蛋白。与PDMA刷子不同,流动条件不影响PMPC和PHPMA刷子上蛋白质电晕的组成。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。载脂蛋白B-100和补体蛋白分别是在流动和静态条件下在PMPC和PHPMA表面上看到的最丰富的蛋白。与PDMA刷子不同,流动条件不影响PMPC和PHPMA刷子上蛋白质电晕的组成。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。载脂蛋白B-100和补体蛋白分别是在流动和静态条件下在PMPC和PHPMA表面上看到的最丰富的蛋白。与PDMA刷子不同,流动条件不影响PMPC和PHPMA刷子上蛋白质电晕的组成。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。在流动条件下形成的蛋白质电晕的性质影响了血小板和红细胞的结合。剪切应力对富含血小板的血浆和全血的血小板粘附的依赖性突出了红细胞在高剪切条件下增强血小板在表面上的粘附的作用。

更新日期:2018-03-08
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