Spatially regulated mRNA translation enables functional membrane protein integration in synthetic cells
Abstract
Synthetic cells aim to emulate living systems by reconstituting essential cellular processes within lipid-bound architectures. However, their functional complexity remains constrained by a key challenge: the synthesis and correct integration of hydrophobic membrane proteins via cell-free approaches. Here, inspired by natural cells, we developed a spatially regulated translation strategy in which membrane-anchored mRNAs recruit ribosomes to drive the cotranslational insertion of membrane proteins into lipid bilayers. This design enables efficient in situ synthesis and integration of multiple transmembrane proteins within giant unilamellar vesicles, supporting selective small-molecule transport across membranes. Importantly, the method allows for precise stoichiometric control of membrane protein composition. Together, this work establishes a minimal yet versatile framework for the direct synthesis and integration of membrane proteins, advancing the construction of functional synthetic cells.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Hang Fu
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics
Lijuan Ma
Jiangsu Key Laboratory for Biomass-Based Energy and Enzyme Technology, School of Chemistry and Chemical Engineering
Chunhua Xu
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics
Jinghua Li
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences
Haochen Ouyang
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences
Congbao Xie
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences
Yunhai Sun
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences
Yuanxiao Tao
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences
Hao Wang
Division of Quantitative Sciences, Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA
Shuxin Hu
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics
Meifang Fu
University of Chinese Academy of Sciences
Hai Zheng
Honghong Zhang
University of Chinese Academy of Sciences
Chenli Liu
State Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Fangfu Ye
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health)
Yan Qiao
Ming Li
Ying Lu