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用于免疫细胞信号空间靶向的功能化表面阵列

Functionalized surface arrays for spatial targeting of immune cell signaling.

作者信息

Senaratne Wageesha, Sengupta Prabuddha, Jakubek Vladimir, Holowka David, Ober Christopher K, Baird Barbara

机构信息

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.

出版信息

J Am Chem Soc. 2006 May 3;128(17):5594-5. doi: 10.1021/ja058701p.

Abstract

The effect of surface topography and chemistry on cellular response is of fundamental importance, especially where living systems encounter device surfaces as in medical implants, tissue engineering, and cell-based sensors. To understand these biological processes on surfaces, there is a widespread interest in tailored surface-active materials produced by a combination of surface chemistry coupled to advanced patterning processes. We utilize self-assembled monolayers (SAMs) as molecular templates with submicrometer-scale spatial resolution to engage and cluster IgE receptors on rat basophilic leukemia (RBL) mast cells. Bioactive templates consisted of gold arrays on silicon with patterns from 1 mum down to 45 nm. These gold arrays served as molecular tethering sites, enabling covalent binding of functionalized self-assembled monolayers of alkanethiols. The free ends of the monolayers were functionalized with 2,4-dinitrophenyl(DNP)-caproate-based ligands which interact specifically with anti-DNP IgE bound to its high affinity cell surface receptor, FcepsilonRI on RBL mast cells. Present results on structures 1 mum down to 600 nm in size indicate that these ligand-immobilized patterned arrays can function as a powerful tool for visualization and systematic characterization of cell membrane involvement in IgE receptor-mediated immune cell signaling.

摘要

表面形貌和化学性质对细胞反应的影响至关重要,尤其是在生物系统与医疗植入物、组织工程和基于细胞的传感器等设备表面接触的情况下。为了理解表面上的这些生物过程,人们对通过表面化学与先进的图案化工艺相结合生产的定制表面活性材料有着广泛的兴趣。我们利用自组装单分子层(SAMs)作为具有亚微米级空间分辨率的分子模板,来结合并聚集大鼠嗜碱性白血病(RBL)肥大细胞上的IgE受体。生物活性模板由硅上的金阵列组成,图案尺寸从1微米到45纳米不等。这些金阵列作为分子连接位点,使链烷硫醇功能化的自组装单分子层能够共价结合。单分子层的自由端用基于2,4 -二硝基苯基(DNP) -己酸酯的配体进行功能化,这些配体与结合在RBL肥大细胞高亲和力细胞表面受体FcepsilonRI上的抗DNP IgE特异性相互作用。目前关于尺寸从1微米到600纳米的结构的结果表明,这些固定有配体的图案化阵列可以作为一种强大的工具,用于可视化和系统地表征细胞膜在IgE受体介导的免疫细胞信号传导中的作用。

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