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A Material-Based Platform to Modulate Fibronectin Activity and Focal Adhesion Assembly

机译:基于材料的平台,以调节纤连蛋白的活性和黏附大会。

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We present a detailed characterization of fibronectin (FN) adsorption and cell adhesion on poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA), two polymers with very similar physicochemical properties and chemical structure, which differ in one single methyl group in the lateral chain of the polymer. The globular solution conformation of FN was retained following adsorption onto PMA, whereas spontaneous organization of FN into protein (nano) networks occurred on PEA. This distinct distribution of FN at the material interface promoted a different availability, measured via monoclonal antibody binding, of two domains that facilitated integrin binding to FN: FNIII10 (RGD sequence) and FNIII9 (PHSRN synergy sequence). The enhanced exposure of the synergy domain on PEA compared to PMA triggered different focal adhesion assemblies: L929 fibroblasts showed a higher fraction of smaller focal plaques on PMA (40%) than on PEA (20%). Blocking experiments with monoclonal antibodies against FNIII10 (HFN7.1) and FNIII9 (mAb1937) confirmed the ability of these polymeric substrates to modulate FN conformation. Overall, we propose a simple and versatile material platform that can be used to tune the presentation of a main extracellular matrix protein (FN) to cells, for applications than span from tissue engineering to disease biology.
机译:我们对纤连蛋白(FN)的吸附和细胞粘附在聚丙烯酸乙酯(PEA)和聚丙烯酸甲酯(PMA)上进行了详细的表征,这两种聚合物具有非常相似的理化性质和化学结构,不同之处在于单个甲基聚合物侧链中的基团。 FN的球状溶液构象在吸附到PMA上后得以保留,而FN的自发组织成为PEA上的蛋白质(纳米)网络。 FN在物质界面的这种独特分布促进了通过单克隆抗体结合测量的两个促进整合素与FN结合的域的不同可用性:FNIII 10 (RGD序列)和FNIII 9 < / sub>(PHSRN协同序列)。与PMA相比,PEA上协同域的增强暴露引发了不同的粘着斑集结:L929成纤维细胞在PMA上(40%)显示出比PEA(20%)更高的较小斑块。用针对FNIII 10 (HFN7.1)和FNIII 9 (mAb1937)的单克隆抗体进行的封闭实验证实了这些聚合物底物调节FN构象的能力。总体而言,我们提出了一个简单而通用的材料平台,该平台可用于调整主要细胞外基质蛋白(FN)向细胞的表达,其应用范围从组织工程到疾病生物学。

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