Defined surface immobilization of glycosaminoglycan molecules for probing and modulation of cell-material interactions.
Defined surface immobilization of glycosaminoglycan molecules for probing and modulation of cell-material interactions.
复制标题
DOI：
10.1021/bm4004942
复制
发表时间：
2013-06
影响因子：
6.2
通讯作者：
Kai Wang;Ying Luo
中科院分区：
文献类型：
--
作者：
Kai Wang;Ying Luo
糖胺聚糖（glycosaminoglycans，GAGs）作为细胞表面和细胞外基质（extracellular matrix，ECM）中一类重要的生物分子，在生物医学领域有着广泛的应用。在理解GAG的生物学功能由生理和病理过程的复杂动力学驱动的情况下，期望方法学允许以分子水平的精确度阐明细胞-GAG相互作用。在这项研究中，通过一种新的表面改性策略，涉及聚多巴胺（PDA）和GAG分子功能化与酰肼化学基团的微量滴定板为基础的系统。包括透明质酸（具有不同分子量）、肝素和硫酸软骨素的GAG的小文库在容易的水性条件下通过限定的结合位点成功地固定到微量滴定板表面上。然后，该方法允许以高通量格式对GAG改性表面进行平行研究。结果表明，固定化的GAG具有不同的属性，介导蛋白质吸附，细胞粘附和炎症反应，与每个属性显示依赖于特定的GAG分子的类型和分子量。PDA辅助的酰肼官能化GAG的固定允许GAG分子的仿生附着并保留其生物活性，提供了一种新的方法来系统地探测基本细胞-GAG相互作用以调节生物材料的生物活性和生物相容性。
As one important category of biological molecules on the cell surface and in the extracellular matrix (ECM), glycosaminoglycans (GAGs) have been widely studied for biomedical applications. With the understanding that the biological functions of GAGs are driven by the complex dynamics of physiological and pathological processes, methodologies are desired to allow the elucidation of cell-GAG interactions with molecular level precision. In this study, a microtiter plate-based system was devised through a new surface modification strategy involving polydopamine (PDA) and GAG molecules functionalized with hydrazide chemical groups. A small library of GAGs including hyaluronic acid (with different molecular weights), heparin, and chondroitin sulfate was successfully immobilized via defined binding sites onto the microtiter plate surface under facile aqueous conditions. The methodology then allowed parallel studies of the GAG-modified surfaces in a high-throughput format. The results show that immobilized GAGs possess distinct properties to mediate protein adsorption, cell adhesion, and inflammatory responses, with each property showing dependence on the type and molecular weight of specific GAG molecules. The PDA-assisted immobilization of hydrazide-functionalized GAGs allows biomimetic attachment of GAG molecules and retains their bioactivity, providing a new methodology to systematically probe fundamental cell-GAG interactions to modulate the bioactivity and biocompatibility of biomaterials.