Intracellular construction of topology-controlled polypeptide nanostructures with diverse biological functions

Nature Communications
Li-Li LiHao Wang

Abstract

Topological structures of bio-architectonics and bio-interfaces play major roles in maintaining the normal functions of organs, tissues, extracellular matrix, and cells. In-depth understanding of natural self-assembly mechanisms and mimicking functional structures provide us opportunities to artificially control the natural assemblies and their biofunctions. Here, we report an intracellular enzyme-catalyzed polymerization approach for efficient synthesis of polypeptides and in situ construction of topology-controlled nanostructures. We reveal that the phase behavior and topological structure of polypeptides are encoded in monomeric peptide sequences. Next, we elucidate the relationship between polymerization dynamics and their temperature-dependent topological transition in biological conditions. Importantly, the linearly grown elastin-like polypeptides are biocompatible and aggregate into nanoparticles that exhibit significant molecular accumulation and retention effects. However, 3D gel-like structures with thermo-induced multi-directional traction interfere with cellular fates. These findings allow us to exploit new nanomaterials in living subjects for biomedical applications.

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Citations

May 17, 2018·Chemistry : a European Journal·Ruibing AnHong Liu
Jul 28, 2018·Chemical Communications : Chem Comm·Simin WeiYuan Gao
Aug 7, 2018·Advanced Healthcare Materials·Lingyun ZhouShu Wang
Aug 24, 2018·Advanced Healthcare Materials·Kuo ZhangHao Wang
Jul 9, 2020·Chemical Communications : Chem Comm·Yafeng WuSongqin Liu
Nov 18, 2018·Advanced Materials·Qingxin YaoYuan Gao
Oct 25, 2020·Science Advances·Miaomiao ZhangGaolin Liang
Feb 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paolo DogniniFrancesca Giuntini
Aug 20, 2020·Chemical Reviews·Hongjian HeBing Xu
Feb 26, 2019·Journal of the American Chemical Society·Dong-Bing ChengHao Wang
Mar 4, 2020·ACS Central Science·Wenqi YuHuile Gao
Feb 8, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Jin ZhouHao Wang

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Methods Mentioned

BETA
fluorescence resonance
FRET
differential scanning calorimetry
fluorescent resonance energy transfer
fluorescence imaging
xenograft
FACS
flow cytometry
protein assay
thermoprecipitation

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