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Carbon Nanotubes Promote the Development of Intestinal Organoids through Regulating Extracellular Matrix Viscoelasticity and Intracellular Energy Metabolism
ACS Nano ( IF 17.1 ) Pub Date : 2021-10-08 , DOI: 10.1021/acsnano.1c03707
Lin Bao 1, 2 , Xuejing Cui 1, 3 , Xiaoyu Wang 1, 2 , Junguang Wu 1, 2 , Mengyu Guo 1 , Na Yan 1, 2 , Chunying Chen 1, 2, 3
Affiliation  

The biological effect of engineered carbon nanotubes (CNTs) as beneficial biomaterials on the intestine, especially on its development, remains unclear. Here, we investigated the profitable effect of CNTs with a different graphene layer and surface modification on the 3D model of intestinal organoids and demonstrated that CNTs (50 μg/mL) promoted the development of intestinal organoids over time (0–5 days). The mechanisms involve the modulation of extracellular matrix (ECM) viscoelasticity and intracellular energy metabolism. In particular, CNTs reduced the hardness of the extracellular matrix through decreasing the elasticity and increasing the viscosity as a result of elevated metalloproteinase and binding to a protein scaffold, which activated the mechanical membrane sensors of cells, Piezo, and downstream P-p38-yes-associated protein (YAP) pathway. Moreover, CNTs altered the metabolic profile of intestinal organoids and induced increased mitochondria activity, respiration, and nutrient absorption. These mechanisms cooperated with each other to promote the proliferation and differentiation of intestinal organoids. In addition, the promoted effect of CNTs is highly dependent on the number of graphene layers, manifested as multiwalled CNTs > single-walled CNTs. Our findings highlight the CNT–intestine interaction and imply the potential of CNTs as biomaterials for intestine-associated tissue engineering.

中文翻译:

碳纳米管通过调节细胞外基质粘弹性和细胞内能量代谢促进肠道类器官的发育

工程碳纳米管 (CNT) 作为有益生物材料对肠道的生物效应,尤其是对其发育的影响尚不清楚。在这里,我们研究了具有不同石墨烯层和表面改性的 CNT 对肠道类器官 3D 模型的有利影响,并证明 CNT(50 μg/mL)随着时间的推移(0-5 天)促进了肠道类器官的发育。该机制涉及细胞外基质 (ECM) 粘弹性和细胞内能量代谢的调节。特别是,由于金属蛋白酶升高并与蛋白质支架结合,碳纳米管通过降低弹性和增加粘度来降低细胞外基质的硬度,从而激活细胞的机械膜传感器 Piezo,和下游 P-p38-yes 相关蛋白 (YAP) 通路。此外,碳纳米管改变了肠道类器官的代谢特征,并诱导线粒体活性、呼吸和营养吸收增加。这些机制相互配合,促进了肠道类器官的增殖和分化。此外,碳纳米管的促进作用高度依赖于石墨烯层的数量,表现为多壁碳纳米管>单壁碳纳米管。我们的研究结果突出了碳纳米管-肠道相互作用,并暗示碳纳米管作为肠道相关组织工程的生物材料的潜力。这些机制相互配合,促进了肠道类器官的增殖和分化。此外,碳纳米管的促进作用高度依赖于石墨烯层的数量,表现为多壁碳纳米管>单壁碳纳米管。我们的研究结果突出了碳纳米管-肠道相互作用,并暗示碳纳米管作为肠道相关组织工程的生物材料的潜力。这些机制相互配合,促进了肠道类器官的增殖和分化。此外,碳纳米管的促进作用高度依赖于石墨烯层的数量,表现为多壁碳纳米管>单壁碳纳米管。我们的研究结果突出了碳纳米管-肠道相互作用,并暗示碳纳米管作为肠道相关组织工程的生物材料的潜力。
更新日期:2021-10-26
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