Integrin interactions with immobilized peptides in polyethylene glycol diacrylate hydrogels
Integrin interactions with immobilized peptides in polyethylene glycol diacrylate hydrogels
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DOI：
10.1089/ten.2004.10.1775
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发表时间：
2004-11-01
影响因子：
--
通讯作者：
Smith, CW
中科院分区：
文献类型：
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作者：
Gonzalez, AL;Gobin, AS;Smith, CW
本研究采用组织工程技术来评估中性粒细胞与细胞外基质（ECM）模拟肽的相互作用。我们已经使用聚乙二醇（PEG）二丙烯酸酯衍生物来形成水凝胶作为生物惰性表面。生物活性部分与水凝胶的共价连接使其具有生物活性。我们的目标是确定这些部分影响中性粒细胞与这种生物活性水凝胶的相互作用的机制，从而了解ECM中类似配体的可能作用。目前的实验分析了分离的人中性粒细胞与用Arg-Gly-Asp-Ser（RGDS）（一些β（1）和β（3）整联蛋白的已知配体）和Thr-Met-Lys-Ile-Ile-Pro-Phe-Asn-Arg-Leu-Thr-Ile-Gly-Gly（TMKIIPFNRLTIGG）（Mac-1（β（2）整联蛋白）的配体）修饰的PEG水凝胶的相互作用。我们的研究结果表明，中性粒细胞，独立的趋化刺激，表现出很小的能力，坚持未改性的PEG水凝胶。然而，细胞粘附和铺展在肽修饰的水凝胶上是稳健的。单独或组合地阐明不同的生物活性肽使得能够识别α（v）、β（3）、β（1）和β（2）整联蛋白对中性粒细胞粘附和扩散的不同功能。组合的相互作用导致的活性与单独参与整合素的活性明显不同。该模型允许调查特定的配体诱导的白细胞功能和开发具有确定的生物活性特性的工程基质。
This study employs tissue-engineering technologies to evaluate neutrophil interactions with extracellular matrix (ECM)-mimetic peptides. We have used a polyethylene glycol ( PEG) diacrylate derivative to form a hydrogel as a biologically inert surface. Covalent attachment of bioactive moieties to the hydrogel makes it bioactive. The goal is to define the mechanisms by which these moieties influence the interactions of neutrophils with this bioactive hydrogel, and thus understand the likely effects of similar ligands in the ECM. The current experiments analyze the interactions of isolated human neutrophils with PEG hydrogels modified with Arg-Gly-Asp-Ser (RGDS), a known ligand for some beta(1) and beta(3) integrins, and Thr-Met-Lys-Ile-Ile-Pro-Phe-Asn-Arg-Leu-Thr-Ile-Gly-Gly (TMKIIPFNRLTIGG), a ligand for Mac-1, a beta(2) integrin. Our results demonstrate that neutrophils, independent of chemotactic stimulation, show little ability to adhere to unmodified PEG hydrogels. However, cell adhesion and spreading are robust on peptide-modified hydrogels. Incorporating distinct bioactive peptides, either alone or in combination, has enabled recognition of differential functions of alpha(v)beta(3), beta(1), and beta(2) integrins on neutrophil adhesion and spreading. Combined interactions result in activity that differs markedly from that seen with either integrin independently engaged. This model allows investigation of specific ligand-induced leukocyte functions and the development of engineered matrices with defined bioactive properties.