Synthetic Chemoselective Rewiring of Cell Surfaces: Generation of Three-Dimensional Tissue Structures
Synthetic Chemoselective Rewiring of Cell Surfaces: Generation of Three-Dimensional Tissue Structures
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DOI：
10.1021/ja2022569
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发表时间：
2011-06-08
影响因子：
15
通讯作者：
Yousaf, Muhammad N.
中科院分区：
文献类型：
--
作者：
Dutta, Debjit;Pulsipher, Abigail;Yousaf, Muhammad N.
通过物理接触进行的适当的细胞通信对于一系列基本生物过程（包括细胞增殖、迁移、分化和凋亡）以及对于器官和其他多细胞组织的正确功能是至关重要的。体内这些细胞相互作用的空间和时间安排是动态的，并导致在体外极难重现的高阶功能。三维（3D），在体外模型系统的发展，以调查这些复杂的，在体内的相互联系将产生新的方法来研究这些过程的生化信号，以及提供组织工程技术的平台。在此，我们开发并采用了一种策略，通过基于脂质体递送和融合的化学选择性细胞表面工程来诱导3D中特异性和稳定的细胞-细胞接触，以显示来自细胞膜的生物正交官能团。该策略使用脂质体融合将酮或羟胺基团递送至不同的细胞群体，用于随后通过肟连接进行细胞组装。我们展示了这种方法如何可以用于几个应用程序，包括，交付试剂的细胞荧光标记和细胞表面工程，形成小的，3D球状体细胞组件，并产生大而密集的，3D多层组织样结构的组织工程应用。
Proper cell cell communication through physical contact is crucial for a range of fundamental biological processes including, cell proliferation, migration, differentiation, and apoptosis and for the correct function of organs and other multicellular tissues. The spatial and temporal arrangements of these cellular interactions in vivo are dynamic and lead to higher-order function that is extremely difficult to recapitulate in vitro. The development of three-dimensional (3D), in vitro model systems to investigate these complex, in vivo interconnectivities would generate novel methods to study the biochemical signaling of these processes, as well as provide platforms for tissue engineering technologies. Herein, we develop and employ a strategy to induce specific and stable cell-cell contacts in 3D through chemoselective cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. This strategy uses liposome fusion for the delivery of ketone or oxyamine groups to different populations of cells for subsequent cell assembly via oxime ligation. We demonstrate how this method can be used for several applications including, the delivery of reagents to cells for fluorescent labeling and cell-surface engineering, the formation of small, 3D spheroid cell assemblies, and the generation of large and dense, 3D multilayered tissue-like structures for tissue engineering applications.