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细菌磁小体作为新型平台用于在细胞生物技术中展示免疫刺激性、膜结合配体。

Bacterial Magnetosomes as Novel Platform for the Presentation of Immunostimulatory, Membrane-Bound Ligands in Cellular Biotechnology.

机构信息

Department Microbiology, University of Bayreuth, Universitätsstraße 30, D-95447, Bayreuth, Germany.

Department Process Biotechnology, University of Bayreuth, Universitätsstraße 30, D-95447, Bayreuth, Germany.

出版信息

Adv Biosyst. 2020 Mar;4(3):e1900231. doi: 10.1002/adbi.201900231. Epub 2020 Feb 7.

Abstract

Cell-cell interactions involving specific membrane proteins are critical triggers in cellular development. Ex vivo strategies to mimic these effects currently use soluble proteins or (recombinant) presenter cells, albeit with mixed results. A promising alternative are bacterial magnetosomes, which can be selectively transformed into cell-free membrane-protein presenters by genetic engineering. In this study, the human CD40 Ligand (CD40L), a key ligand for B cell activation, is expressed on the particle surface. Functionality is demonstrated on sensor cells expressing the human CD40 receptor. Binding of CD40L magnetosomes to these cells triggers a signaling cascade leading to the secretion of embryonic alkaline phosphatase. Concomitantly, the CD40-CD40L interaction is strong enough to allow cell recovery by magnetic sorting. Overall, this study demonstrates the potential of magnetosomes as promising cell-free tools for cellular biotechnology, based on the display of membrane-bound target molecules, thereby creating a biomimetic interaction.

摘要

涉及特定膜蛋白的细胞间相互作用是细胞发育的关键触发因素。目前,模拟这些效应的体外策略使用可溶性蛋白或(重组)呈递细胞,但结果喜忧参半。一种很有前途的替代方法是细菌磁小体,它可以通过基因工程选择性地转化为无细胞膜蛋白呈递体。在这项研究中,人 CD40 配体 (CD40L) 是 B 细胞激活的关键配体,在颗粒表面表达。在表达人 CD40 受体的传感器细胞上证明了其功能。CD40L 磁小体与这些细胞的结合触发信号级联反应,导致胚胎碱性磷酸酶的分泌。同时,CD40-CD40L 相互作用足够强,可以通过磁分选回收细胞。总的来说,这项研究基于展示膜结合靶分子,展示了磁小体作为细胞生物技术有前途的无细胞工具的潜力,从而创造了一种仿生相互作用。

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