The microenvironment of immobilized Arg-Gly-Asp peptides is an important determinant of cell adhesion
The microenvironment of immobilized Arg-Gly-Asp peptides is an important determinant of cell adhesion
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DOI：
10.1016/s0142-9612(00)00259-3
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发表时间：
2001-05-01
期刊：
影响因子：
14
通讯作者：
Mrksich, M
中科院分区：
文献类型：
--
作者：
Houseman, BT;Mrksich, M
本文使用自组装单分子膜作为模型系统，以证明瑞士3 T3成纤维细胞的附着和扩散强烈依赖于固定化的RGD肽的微环境。这项工作利用的单层，目前的混合物的Arg-Gly-Asp肽，这是细胞整合素受体的配体，和寡（乙二醇）基团，这抵抗蛋白质的非特异性吸附。肽配体的微环境通过改变单层上周围寡（乙二醇）基团的长度来控制。通过使用存在三-、四-、五-或六（乙二醇）单元的硫醇，二醇基团和肽配体之间的平均距离被改变，而背景的结构和性质保持不变。随着寡聚（乙二醇）组长度的增加，细胞附着到呈现固定密度的肽的单层减少。贴壁细胞的平均投影面积显示出类似的趋势。在较低密度的固定化肽，细胞附着和投影细胞面积的减少更明显。附着和扩散不依赖于三（乙二醇）基团的单层上的肽的密度，但表现出较高的灵敏度，单层上的配体的密度提出较长的乙二醇低聚物。使用可溶性肽来抑制细胞与单层的附着的实验表明，细胞-基质相互作用的强度在呈现较长二醇基团的单层上降低。总之，这些结果表明，肽配体的微环境影响的整合素肽相互作用的亲和力和较弱的相互作用显示密度依赖性增强的细胞附着和扩散过程中的结合。这一发现是将生物学功能与底物上配体组成相关联的研究中的重要考虑因素。这一发现也代表了生物活性材料设计的重要原则，因为它说明了粘附基序的呈现可以改变哺乳动物细胞反应的程度。(C)2001爱思唯尔科技有限公司版权所有。
This paper uses self-assembled monolayers on gold as a model system to demonstrate that the attachment and spreading of Swiss 3T3 fibroblasts depends strongly on the microenvironment of immobilized RGD peptides. This work utilized monolayers that present mixtures of Arg-Gly-Asp peptides, which are ligands for cellular integrin receptors, and oligo(ethylene glycol) groups, which resist the nonspecific adsorption of protein. The microenvironment of the peptide ligands was controlled by altering the length of the surrounding oligo(ethylene glycol) groups on the monolayer. By using thiols that present either tri-, tetra-, penta-, or hexa(ethylene glycol) units, the average distance separating the glycol groups and the peptide ligand is altered while the structure and properties of the background remain unchanged. Cell attachment to monolayers presenting a fixed density of peptide decreased as the length of the oligo(ethylene glycol) group increased. The average projected area of attached cells showed a similar trend. At lower densities of immobilized peptide, decreases in both cell attachment and projected cell area were more pronounced. Attachment and spreading did not depend on density of peptide on monolayers presenting tri(ethylene glycol) groups, but showed a high sensitivity to density of ligand on monolayers presenting longer glycol oligomers. Experiments that used a soluble peptide to inhibit the attachment of cells to monolayers demonstrated that the strength of the cell-substrate interaction decreased on monolayers presenting longer glycol groups. Together, these results suggest that the microenvironment of the peptide ligand influences the affinity of the integrin-peptide interaction and that weaker interactions display a density-dependent enhancement of binding during cell attachment and spreading. This finding is an important consideration in studies that correlate biological function with the composition of ligands on a substrate. This finding also represents an important principle for the design of biologically active materials because it illustrates the degree to which the presentation of adhesion motifs can modify the response of mammalian cells. (C) 2001 Elsevier Science Ltd. All rights reserved.