Supramolecular approaches to combining membrane transport with adhesion.
Supramolecular approaches to combining membrane transport with adhesion.
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DOI：
10.1021/ar400032c
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发表时间：
2013-12-17
影响因子：
18.3
通讯作者：
Webb, Simon J.
中科院分区：
文献类型：
--
作者：
Webb, Simon J.
细胞利用对化学刺激作出反应的“门控”蛋白质通道，小心地控制化合物通过细胞膜的转运。连接蛋白间隙连接是一类具有多层次组装的门控通道，是高电导的细胞间通道。粘附细胞之间的间隙连接包括每个细胞膜中的两个半通道，其彼此粘附以形成连续的细胞-细胞通道。每个半通道是六个蛋白质跨膜亚基的六聚体组装。这些间隙连接显示膜内组装和膜间组装，使它们成为仿生研究的一个有吸引力的目标。虽然已经开发了许多自组装通道的例子，但很少有也可以介导膜间粘附。开发将联合收割机膜粘附与跨膜受控运输相结合的系统不仅可以更好地理解膜内和膜周围的自组装，而且还可以提供一条通往智能生物材料、靶向药物递送和与纳米技术接口的途径。这个帐户描述了我们的仿生方法，结合膜粘附与膜运输，使用自组装的“粘性”孔和“粘性”纳米粒子触发跨膜运输。这种结合将基础研究和应用研究联系起来，作为分子水平组装和功能生物材料形成之间的桥梁。最终目标是在生物或仿生环境中创建复杂的自组装系统，该系统可以与细胞相互作用，并响应远程化学或电磁信号将化合物跨双层运输。我们在这一领域的研究始于膜内和膜间自组装的基础研究，建立在以前已知的通道形成化合物，以创建可切换或能够介导囊泡-囊泡粘附的自组装通道。随后，具有“粘性”涂层的纳米颗粒用于介导囊泡之间的粘附。将这些粘合剂特性与纳米级磁铁矿的独特特性相结合，允许非侵入性的磁信号触发化合物从磁性纳米颗粒-囊泡组件中运输出来。添加囊外基质产生了用于组织工程的新的响应性生物材料。这些生物材料可以被磁性图案化，并且可以在接收到磁信号时递送药物，从而允许对细胞反应进行时空控制。
Cells carefully control the transit of compounds through their membranes using “gated” protein channels that respond to chemical stimuli. Connexin gap junctions, which are high conductance cell-to-cell channels, are a remarkable class of “gated” channel with multiple levels of assembly. A gap junction between adhering cells comprises two half-channels in each cell membrane that adhere to each other to form a continuous cell-to-cell channel. Each half-channel is a hexameric assembly of six protein transmembrane subunits. These gap junctions display both intramembrane assembly and intermembrane assembly, making them an attractive target for biomimetic studies. Although many examples of self-assembled channels have been developed, few can also mediate intermembrane adhesion. Developing systems that combine membrane adhesion with controlled transit across the membrane would not only provide a better understanding of self-assembly in and around the membrane, but would also provide a route towards smart biomaterials, targeted drug delivery and an interface with nanotechnology. This Account describes our biomimetic approaches to combining membrane adhesion with membrane transport, using both self-assembled “sticky” pores and “sticky” nanoparticles to trigger transit across membranes. This combination links both fundamental and applied research, acting as a bridge between molecular level assembly and the formation of functional biomaterials. The ultimate goal is to create complex self-assembled systems in biological or biomimetic environments that can both interface with cells and transport compounds across bilayers in response to remote chemical or electromagnetic signals. Our research in this area started with fundamental studies of intramembrane and intermembrane self-assembly, building upon previously known channel-forming compounds to create self-assembled channels that were switchable or able to mediate vesicle–vesicle adhesion. Subsequently, nanoparticles with a “sticky” coating were used to mediate adhesion between vesicles. Combining these adhesive properties with the unique characteristics of nanosized magnetite allowed a noninvasive magnetic signal to trigger transport of compounds out of magnetic nanoparticle-vesicle assemblies. Adding an extravesicular matrix produced new responsive biomaterials for use in tissue engineering. These biomaterials can be magnetically patterned and can deliver drugs upon receipt of a magnetic signal, allowing spatiotemporal control over cellular responses.
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