哈尔滨工业大学化工与化学学院,城乡水资源与水环境全国重点实验室,黑龙江省分子科学联合实验室(国际合作),黑龙江 哈尔滨 150001
刘延浩(1996—),男,博士研究生。研究方向为人造细胞、合成生物学。
韩晓军(1975—),男,教授,博士,博士生导师。研究方向人造细胞、合成生物学、癌症诊疗、药物控释、污染物检测与降解、生物传感器等。
收稿:2026-08-05,
修回:2026-10-21,
网络首发:2026-10-23,
移动端阅览
刘延浩, 韩晓军. 具有信号转导功能的人造细胞及其应用进展[J]. 合成生物学, 2026, 7. DOI: 10.12211/2096-8280.2026-074
LIU Yanhao, HAN Xiaojun. Research progress in artificial cells capable of signal transduction and their applications[J]. Synthetic Biology Journal, 2026, 7. DOI: 10.12211/2096-8280.2026-074
人造细胞的跨膜信号转导是自主人造细胞的核心功能。构建具有信号转导功能的人造细胞面临信号转导能力有限、与下游代谢耦合不足等诸多挑战。本文系统介绍了人造细胞信号转导的三大类载体,包括生物大分子、合成分子及纳米结构,描述了各类信号转导载体的原理、功能特性与最新研究进展。生物大分子体系依托天然离子通道与G蛋白偶联受体的功能性重组,实现化学、机械及激素信号的转导;合成分子体系通过化学修饰实现离子通道与合成受体的可编程设计;纳米结构体系依托DNA纳米组装体与碳纳米管孔蛋白的可编程性,实现信号转导与群落通讯。分析了具有信号转导功能人造细胞在高灵敏生物传感、疾病治疗及生物逻辑计算等领域的应用现状,指出目前存在信号整合能力不足、能量无法自给、体内稳定性欠佳、规模化制备难度大等核心瓶颈问题,提出了构建模块化反馈调控网络、耦合能量供给系统、优化膜组分与制备工艺等针对性解决方案,并对多细胞协同信号转导体系研发及临床转化的未来发展方向进行了展望。
Transmembrane signal transduction in artificial cells is a core function of autonomous artificial cells. However
the construction of artificial cells capable of signal transduction has faced multiple challenges
such as limited signal transduction capacity and insufficient coupling with downstream metabolic pathways. In this review
we summarize three major categories of signal transduction carriers for artificial cells
including biomacromolecules
synthetic molecules
and nano-biomimetic structures
and describe their working mechanisms
functional characteristics
and latest research progress. Biomacromolecule-based systems rely on functional reconstitution of natural ion channels and G protein-coupled receptors. α-hemolysin forms stable transmembrane nanopores for small molecule transport
supporting intercellular chemical communication and intracellular genetic circuit activation. Mechanosensitive channels mediate calcium influx in response to membrane tension for mechanosensing. Notably
a reconstituted β2-adrenergic receptor pathway achieves GPCR-mediated glycogen metabolism regulation via the second messenger cAMP
marking key progress in coupling transmembrane signaling to intracellular metabolism. Synthetic molecule-based systems overcome the limitations of natural proteins through chemical design. Synthetic ion channels
including organic macrocycles and peptide foldamers
enable programmable
stimuli-responsive ion transport with responsiveness to light
pH and metal ions. Synthetic receptors transduce extracellular signals into intracellular outputs via conformational change
dimerization
membrane translocation and energy conversion mechanisms. Nanostructure-based systems feature high programmability. DNA origami assemblies precisely regulate membrane permeability and mediate intercellular communication via strand displacement reactions. Carbon nanotube porins form uniform cation-selective channels with high ion flux for efficient transmembrane signal delivery. Leveraging these diverse signaling modules
artificial cells have shown broad application prospects in highly sensitive biosensing
smart disease therapy and biochemical logic computation. They enable specific target detection in complex matrices
stimulus-responsive therapeutic delivery with reduced off-target effects
and construction of programmable biological logic devices. Nevertheless
critical challenges remain in multi-signal integration
energy autonomy
long-term in vivo stability and scalable standardized manufacturing. Future research should prioritize feedback-regulated signaling networks
energy-autonomous systems
multi-cellular coordinated communication
and scalable fabrication processes to promote the practical translation of artificial cell technologies.
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