Noncovalent cell surface engineering: Incorporation of bioactive synthetic glycopolymers into cellular membranes
Noncovalent cell surface engineering: Incorporation of bioactive synthetic glycopolymers into cellular membranes
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DOI：
10.1021/ja710644g
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发表时间：
2008-05-07
影响因子：
15
通讯作者：
Bertozzi, Carolyn R.
中科院分区：
文献类型：
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作者：
Rabuka, David;Forstner, Martin B.;Bertozzi, Carolyn R.
控制添加结构确定的组分到活细胞膜可以促进细胞表面现象的分子水平分析。在这里，我们证明了细胞表面可以通过外源性膜插入以限定的密度显示合成的生物活性聚合物。这些聚合物被设计成模拟天然细胞表面粘蛋白糖蛋白，其由其密集的糖基化模式和棒状结构定义。用疏水性锚的末端官能化允许掺入活培养细胞的膜中。我们利用荧光相关光谱（FCS）研究了具有不同疏水锚和聚糖结构的细胞结合糖共聚物的动态行为。它们的扩散特性反映了许多天然膜相关生物分子的扩散特性。此外，膜结合的糖聚合物被内化到早期的内体类似的内源性膜成分，并能够与蛋白受体的特异性相互作用。该系统提供了一个研究细胞表面现象的平台，具有一定程度的化学控制，这是使用传统生物工具无法实现的。
The controlled addition of structurally defined components to live cell membranes can facilitate the molecular level analysis of cell surface phenomena. Here we demonstrate that cell surfaces can be engineered to display synthetic bioactive polymers at defined densities by exogenous membrane insertion. The polymers were designed to mimic native cell-surface mucin glycoproteins, which are defined by their dense glycosylation patterns and rod-like structures. End-functionalization with a hydrophobic anchor permitted incorporation into the membranes of live cultured cells. We probed the dynamic behavior of cell-bound glycopolymers bearing various hydrophobic anchors and glycan structures using fluorescence correlation spectroscopy (FCS). Their diffusion properties mirrored those of many natural membrane-associated biomolecules. Furthermore, the membrane-bound glycopolymers were internalized into early endosomes similarly to endogenous membrane components and were capable of specific interactions with protein receptors. This system provides a platform to study cell-surface phenomena with a degree of chemical control that cannot be achieved using conventional biological tools.