Endothelial cell migration on RGD-peptide-containing PEG hydrogels in the presence of sphingosine 1-phosphate
Endothelial cell migration on RGD-peptide-containing PEG hydrogels in the presence of sphingosine 1-phosphate
复制标题
DOI：
10.1529/biophysj.107.109074
复制
发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Elbert, Donald L.
中科院分区：
文献类型：
--
作者：
Wacker, Bradley K.;Alford, Shannon K.;Elbert, Donald L.
1-磷酸鞘氨醇（S1 P）是一种有效的内皮细胞趋化剂，由活化的血小板释放。我们先前开发了含Arg-Gly-Asp（RGD）的聚乙二醇生物材料，用于控制S1 P的递送以促进内皮化。在这里，我们研究了细胞粘附强度对S1 P刺激的内皮细胞迁移的影响，在动脉水平的流体剪切应力的存在下，因为向上移动的最佳细胞粘附强度可能有利于促进长期的细胞粘附材料。将具有不同整合素结合特异性的两种RGD肽添加到聚乙二醇水凝胶中。线性R ⑶主要与β 3整联蛋白结合，而环状R ⑶通过β 1和β 3整联蛋白两者结合。我们观察到增加的粘着斑形成和更好的长期粘附流动与内皮细胞上的线性RGD肽，与环状RGD，即使初始粘附强度较高的细胞上的环状RGD。添加100 nM S1 P增加了细胞速度和随机运动系数的两个RGD肽，最大的增加发现环RGD。对于这两种肽，发现细胞迁移速度的大部分增加是在较小的细胞（< 1522 μ m（2）投影面积）中，尽管环RGD的大幅增加也是由于中等大小的细胞（2288-3519 μ m（2））。总的来说，在植入后内皮化的材料的设计中，高细胞迁移率和长期粘附之间的折衷将是重要的。
Sphingosine 1-phosphate (S1P) is a potent chemokinetic agent for endothelial cells that is released by activated platelets. We previously developed Arg-Gly-Asp (RGD)-containing polyethylene glycol biomaterials for the controlled delivery of S1P to promote endothelialization. Here, we studied the effects of cell adhesion strength on S1P-stimulated endothelial cell migration in the presence of arterial levels of fluid shear stress, since an upward shift in optimal cell adhesion strengths may be beneficial for promoting long-term cell adhesion to materials. Two RGD peptides with different integrin-binding specificities were added to the polyethylene glycol hydrogels. A linear RGD bound primarily to beta 3 integrins, whereas a cyclic RGD bound through both beta 1 and beta 3 integrins. We observed increased focal adhesion formation and better long-term adhesion in flow with endothelial cells on linear RGD peptide, versus cyclic RGD, even though initial adhesion strengths were higher for cells on cyclic RGD. Addition of 100 nM S1P increased cell speed and random motility coefficients on both RGD peptides, with the largest increases found on cyclic RGD. For both peptides, much of the increase in cell migration speed was found for smaller cells (< 1522 mu m(2) projected area), although the large increases on cyclic RGD were also due to medium-sized cells (2288-3519 mu m(2)). Overall, a compromise between high cell migration rates and long-term adhesion will be important in the design of materials that endothelialize after implantation.