Positively and Negatively Modulating Cell Adhesion to Type I Collagen Via Peptide Grafting
Positively and Negatively Modulating Cell Adhesion to Type I Collagen Via Peptide Grafting
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DOI：
10.1089/ten.tea.2008.0346
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发表时间：
2011-07-01
影响因子：
4.1
通讯作者：
Shreiber, David I.
中科院分区：
文献类型：
--
作者：
Monteiro, Gary A.;Fernandes, Anthony V.;Shreiber, David I.
细胞和 I 型胶原之间的生物物理相互作用由细胞粘附水平控制，细胞粘附水平主要由胶原上配体的密度和细胞上整合素受体的密度决定。通过将甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸（GRGDS）（包括生物活性RGD序列）或甘氨酸-精氨酸-天冬氨酸-甘氨酸-丝氨酸（GRDGS）（包括乱序RDG序列）与异双功能偶联剂1-乙基-3-（3-二甲氨基丙基）共价接枝到胶原上，调节胶原蛋白的天然粘附性碳二亚胺。肽接枝胶原自组装成纤维状凝胶，凝胶结构和流变学的变化可以忽略不计。大鼠真皮成纤维细胞 (RDF) 和人平滑肌细胞表现出在由 RGD 接枝胶原制备的凝胶上的粘附水平增加，而在 RDG 接枝胶原上的粘附水平降低。两种细胞类型均表现出压缩自由漂浮的 RGD 接枝胶原凝胶的能力增强，而压缩 RDG 接枝凝胶的能力受损。 RDG 移植的胶原蛋白在胶原蛋白上和胶原蛋白内的 RDF 迁移增加，RGD 移植的胶原蛋白减少，并且剂量反应实验表明 RDF 迁移对粘附的双相反应。平滑肌细胞表现出类似的趋势，尽管在统计上不显着。正向和负向调节细胞与胶原蛋白粘附的能力增加了这种天然生物材料用于再生治疗的多功能性。
The biophysical interactions between cells and type I collagen are controlled by the level of cell adhesion, which is dictated primarily by the density of ligands on collagen and the density of integrin receptors on cells. The native adhesivity of collagen was modulated by covalently grafting glycine-arginine-glycine-aspartic acid-serine (GRGDS), which includes the bioactive RGD sequence, or glycine-arginine-aspartic acid-glycine-serine (GRDGS), which includes the scrambled RDG sequence, to collagen with the hetero-bifunctional coupling agent 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The peptide-grafted collagen self-assembled into a fibrillar gel with negligible changes in gel structure and rheology. Rat dermal fibroblasts (RDFs) and human smooth muscle cells demonstrated increased levels of adhesion on gels prepared from RGD-grafted collagen, and decreased levels of adhesion on RDG-grafted collagen. Both cell types demonstrated an increased ability to compact free-floating RGD-grafted collagen gels, and an impaired ability to compact RDG-grafted gels. RDF migration on and within collagen was increased with RDG-grafted collagen and decreased with RGD-grafted collagen, and dose-response experiments indicated a biphasic response of RDF migration to adhesion. Smooth muscle cells demonstrated similar, though not statistically significant, trends. The ability to both positively and negatively modulate cell adhesion to collagen increases the versatility of this natural biomaterial for regenerative therapies.