通过合成隙受体设计可编程的物质到细胞通路,以空间控制多细胞结构中的分化
Mher Garibyan1,2,3, Tyler Hoffman4, Thijs Makaske1,2,5
1Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Nature communications
|July 13, 2024
概括
研究人员开发了用于控制合成Notch (synNotch) 受体的新材料,使组织工程应用中细胞功能的精确空间控制成为可能.
科学领域:
- 生物材料科学 生物材料科学
- 合成生物学 合成生物学
- 组织工程是组织工程.
背景情况:
- 合成Notch (synNotch) 受体允许细胞感知信号并触发特定的遗传程序.
- 现有的方法为synNotch连接体提供了有限的空间控制,特别是在细胞外基质 (ECM) 支架上,这对组织工程至关重要.
研究的目的:
- 创建用于激活synNotch受体的多功能材料,使材料对细胞信号的精确控制成为可能.
- 通过工程材料-细胞相互作用来控制细胞表型,以微观精度设计组织.
主要方法:
- 从遗传和化学上对ECM蛋白质和ECM衍生材料的synNotch配体进行结合.
- 使用微接触式打印,在表面上模拟两个直角的synNotch连接体.
- 使用两个synNotch程序共同培养细胞,以微小精度实现四种不同的记者表型.
主要成果:
- 成功将synNotch连接物与ECM组件融合,创造了新的信号材料.
- 证明了对细胞表型的微观控制,产生了四个不同的记者输出.
- 通过在定义的微型模式内将纤维细胞联合分化为特定细胞类型,展示了组织工程中的应用.
结论:
- 通过synNotch受体开发了一个材料平台,用于通过synNotch受体进行材料到细胞信号的通用化工程.
- 通过工程材料-连接体相互作用,使哺乳动物组织中细胞表型的精确空间控制成为可能.
- 铺平了再生医学和合成生物学中先进应用的道路.
相关概念视频
03:14Notch Signaling Pathway
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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