Assembling and decorating hyaluronan hydrogels with twin protein superglues to mimic cell-cell interactions.
Assembling and decorating hyaluronan hydrogels with twin protein superglues to mimic cell-cell interactions.
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DOI：
10.1016/j.biomaterials.2018.07.020
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发表时间：
2018-07
期刊：
影响因子：
14
通讯作者：
Robert Wieduwild;M. Howarth
中科院分区：
文献类型：
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作者：
Robert Wieduwild;M. Howarth
简单的聚合物支架对细胞行为产生了巨大的影响。对于更复杂的表型，需要精确和有效的化学方法将蛋白质掺入这些支架中。在这里，我们衍生透明质酸与弹性蛋白样多肽含有遥爪SpyTag（HA-SpyTag）。我们的第二个网络组件，TriCatcher蛋白，有两个SpyCatcher和一个终端SnoopCatcher。混合HA-SpyTag与TriCatcher导致通过自发酰胺化快速形成水凝胶。SnoopCatcher允许通过正交转酰胺作用用SnoopTagJR连接的粘附分子进行模块化网络装饰。这种编程支架能够测试单个基质锚定蛋白质相互作用如何影响细胞行为。上皮细胞粘附分子（EpCAM）调节细胞行为和迁移，在癌症中具有重要作用。EpCAM锚定到水凝胶诱导3D培养中非恶性乳腺球的分解。通过有效的生物相容性化学将信号蛋白整合到生物材料中应该揭示控制细胞行为的关键线索。
Simple polymeric scaffolds have yielded dramatic effects on cell behavior. For more sophisticated phenotypes, precise and efficient chemistries are desired to incorporate proteins into these scaffolds. Here we derivatize hyaluronan with an elastin-like polypeptide containing telechelic SpyTags (HA-SpyTag). Our second network component, the TriCatcher protein, had two SpyCatchers and a terminal SnoopCatcher. Mixing HA-SpyTag with TriCatcher led to rapid hydrogel formation, via spontaneous amidation. SnoopCatcher allowed modular network decoration with SnoopTagJr-linked adhesion molecules, through orthogonal transamidation. This programmed scaffold enables the testing of how individual matrix-anchored protein interactions affect cell behavior. Epithelial cell adhesion molecule (EpCAM) regulates cell behavior and migration, with important effects in cancer. EpCAM-anchoring to the hydrogel induced disassembly of non-malignant mammary spheres in 3D culture. Integrating signaling proteins into biomaterials via efficient biocompatible chemistry should reveal key cues to control cell behavior.