工程可编程材料到细胞途径通过合成口受体以空间控制多细胞结构中的细胞表型
bioRxiv : the preprint server for biology
|June 9, 2023
概括
研究人员开发了用于控制合成Notch (synNotch) 受体的新材料,使组织工程和再生医学应用中细胞的精确空间模式成为可能.
科学领域:
- 合成生物学 合成生物学
- 生物材料工程是生物材料的工程.
- 细胞工程 细胞工程
背景情况:
- 合成Notch (synNotch) 受体使细胞能够通过激活特定的遗传程序来响应来自邻居的信号.
- 目前的synNotch应用受限于细胞呈现的配体,限制了组织工程中的空间控制.
- 开发基于材料的平台对于精确的,用户定义的材料到细胞信号传输至关重要.
研究的目的:
- 开发新的基于材料的平台,以激活具有高空间控制的synNotch受体.
- 为用户定义的细胞反应创建可通用的物质到细胞信号通路.
- 为了实现多细胞系统的精确模式,用于诸如组织工程等应用.
主要方法:
- 通过基因工程将synNotch连接物与细胞外矩阵蛋白 (纤维蛋白) 结合.
- 使用酶和点击化学来将synNotch配体与凝水凝连接起来.
- 使用微接触式打印和微流体图案来实现微尺度控制synNotch激活.
- 工程细胞具有多个synNotch路径,用于复杂的组织模式.
主要成果:
- 证明了synNotch配体与生物材料的成功结合.
- 在细胞单层上实现了微观空间控制synNotch激活.
- 成功地模拟了多达三种不同的细胞表型的组织.
- 在用户定义的空间模式下,共分化纤维细胞成骨肌肉和内皮细胞.
- 带有规定的血管网络的工程肌肉组织.
结论:
- 这项工作将synNotch工具包扩展到多功能基于材料的平台.
- 为哺乳动物系统中细胞表型的空间控制提供了新的方法.
- 在发育生物学,组织建模和再生医学中提供广泛的应用.
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