Cell-binding domain context affects cell behavior on engineered proteins
Cell-binding domain context affects cell behavior on engineered proteins
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DOI：
10.1021/bm049627q
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发表时间：
2005-01-01
影响因子：
6.2
通讯作者：
Tirrell, DA
中科院分区：
文献类型：
--
作者：
Heilshorn, SC;Liu, JC;Tirrell, DA
一个家庭的人工细胞外基质蛋白开发应用于小直径血管移植物，用于检查细胞结合域的情况下，细胞粘附和扩散的重要性。工程化的蛋白质序列衍生自天然存在的细胞外基质蛋白弹性蛋白和纤连蛋白。虽然每个工程化蛋白质含有相同的CS5细胞结合结构域序列，但用作交联位点的赖氨酸残基（i）在弹性蛋白盒内或（ii）局限于蛋白质的末端。内皮细胞在这两种蛋白质中特异性地粘附于CS5序列，但细胞粘附和铺展在赖氨酸残基局限于链的末端区域的蛋白质上更稳健。这些结果可能是由于改变的蛋白质构象影响CS5序列的可接近性或其对内皮细胞表面上的α（4）β（1）整联蛋白受体的亲和力。因此，细胞结合结构域之外的氨基酸选择可以对在人工细胞外基质蛋白上培养的细胞的行为产生显著影响。
A family of artificial extracellular matrix proteins developed for application in small-diameter vascular grafts is used to examine the importance of cell-binding domain context on cell adhesion and spreading. The engineered protein sequences are derived from the naturally occurring extracellular matrix proteins elastin and fibronectin. While each engineered protein contains identical CS5 cell-binding domain sequences, the lysine residues that serve as cross-linking sites are either (i) within the elastin cassettes or (ii) confined to the ends of the protein. Endothelial cells adhere specifically to the CS5 sequence in both of these proteins, but cell adhesion and spreading are more robust on proteins in which the lysine residues are confined to the terminal regions of the chain. These results may be due to altered protein conformations that affect either the accessibility of the CS5 sequence or its affinity for the alpha(4)beta(1), integrin receptor on the endothelial cell surface. Amino acid choice outside the cell-binding domain can thus have a significant impact on the behavior of cells cultured on artificial extracellular matrix proteins.