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

• Published in: Nature communications Vol. 8; no. 1; pp. 1276 - 12
• Main Authors: Li, Li-Li, Qiao, Sheng-Lin, Liu, Wei-Jiao, Ma, Yang, Wan, Dong, Pan, Jie, Wang, Hao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.11.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 639/301/357/341; 639/301/54/990; 639/638/45/953; Biocompatibility; Biomedical materials; Cellular structure; Chemical synthesis; Coding; Construction; Elastin; Extracellular matrix; Humanities and Social Sciences; Interfaces; Intracellular; Mimicry; multidisciplinary; Nanomaterials; Nanoparticles; Nanostructure; Nanotechnology; Organs; Peptides; Polymerization; Polypeptides; Science; Science (multidisciplinary); Self-assembly; Temperature dependence; Topology
• DOI: 10.1038/s41467-017-01296-8
• ISSN: 2041-1723

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. The intracellular topology of a nanostructure plays a major role in its interactions with the cell and accordingly, its biological applications. Here, the authors design peptides that intracellularly polymerize into elastin-like polypeptides and assemble into various topologies, each of which exhibits a distinct set of biological functions.