美国北卡罗来纳大学Freeman, Ronit研究团队报道了设计肽- DNA细胞骨架调节合成细胞的功能。相关研究成果发表在2024年4月23日出版的《自然—化学》。

自下而上的人工细胞工程需要一种可重构的细胞骨架，它可以在不同的位置组织并动态调节其结构和机械性能。

该文中，受大量肌动蛋白结合蛋白及其可逆交联或束丝能力的启发，研究人员设计了一个长度、化合价和几何结构不同的肽-DNA交联剂库。通过DNA杂交结合的肽丝产生具有可调纵横比和力学性能的三角形束。当限制在细胞大小的油包水液滴中时，DNA交联剂设计指导细胞骨架结构，在合成细胞的皮层或管腔内的定位。

可调的空间排列调节有效载荷在液滴内的被动扩散，互补的DNA手柄促使有效载荷在细胞骨架上和细胞骨架外的可逆募集和释放。受DNA熔化温度的调节，热诱导的肽-DNA结构的重新配置触发液滴的形状变形。

总之，肽-DNA结构的模块化设计是实现合成细胞自下而上组装的强大策略。

附：英文原文

Title: Designer peptide–DNA cytoskeletons regulate the function of synthetic cells

Author: Daly, Margaret L., Nishi, Kengo, Klawa, Stephen J., Hinton, Kameryn Y., Gao, Yuan, Freeman, Ronit

Issue&Volume: 2024-04-23

Abstract: The bottom-up engineering of artificial cells requires a reconfigurable cytoskeleton that can organize at distinct locations and dynamically modulate its structural and mechanical properties. Here, inspired by the vast array of actin-binding proteins and their ability to reversibly crosslink or bundle filaments, we have designed a library of peptide–DNA crosslinkers varying in length, valency and geometry. Peptide filaments conjoint through DNA hybridization give rise to tactoid-shaped bundles with tunable aspect ratios and mechanics. When confined in cell-sized water-in-oil droplets, the DNA crosslinker design guides the localization of cytoskeletal structures at the cortex or within the lumen of the synthetic cells. The tunable spatial arrangement regulates the passive diffusion of payloads within the droplets and complementary DNA handles allow for the reversible recruitment and release of payloads on and off the cytoskeleton. Heat-induced reconfiguration of peptide–DNA architectures triggers shape deformations of droplets, regulated by DNA melting temperatures. Altogether, the modular design of peptide–DNA architectures is a powerful strategy towards the bottom-up assembly of synthetic cells.

DOI: 10.1038/s41557-024-01509-w

Source: https://www.nature.com/articles/s41557-024-01509-w