Construction of Organelle‐Like Architecture by Dynamic DNA Assembly in Living Cells

• Published in: Angewandte Chemie International Edition Vol. 59; no. 46; pp. 20651 - 20658
• Main Authors: Guo, Xiaocui, Li, Feng, Liu, Chunxia, Zhu, Yi, Xiao, Nannan, Gu, Zi, Luo, Dan, Jiang, Jianhui, Yang, Dayong
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 09.11.2020
• Edition: International ed. in English
• Subjects: Alkynes - chemistry; Assembly; Cell adhesion & migration; Cell migration; Cells (biology); Construction; Cytoplasm; Cytosine; Cytoskeleton; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA hydrogels; DNA nanotechnology; Humans; Hydrogels; i-motif DNA; Monomers; Nanoparticles; organelle-like structure; Oxides - chemistry; Phosphines - chemistry; self-assembly; Stability; Stereoisomerism; Tentacles; Topology; Transformations; DNA hydrogels; self-assembly; DNA nanotechnology; i-motif DNA; organelle-like structure
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202009387

The design of controllable dynamic systems is vital for the construction of organelle‐like architectures in living cells, but has proven difficult due to the lack of control over defined topological transformation of self‐assembled structures. Herein, we report a DNA based dynamic assembly system that achieves lysosomal acidic microenvironment specifically inducing topological transformation from nanoparticles to organelle‐like hydrogel architecture in living cells. Designer DNA nanoparticles are constructed from double‐stranded DNA with cytosine‐rich stick ends (C‐monomer) and are internalized into cells through lysosomal pathway. The lysosomal acidic microenvironment can activate the assembly of DNA monomers, inducing transformation from nanoparticles to micro‐sized organelle‐like hydrogel which could further escape into cytoplasm. We show how the hydrogel regulates cellular behaviors: cytoskeleton is deformed, cell tentacles are significantly shortened, and cell migration is promoted. Design of controllable dynamic systems to construct organelle‐like architectures is an emerging paradigm for recreating cellular functions and interfering disease process. A dynamic DNA system that achieves lysosomal acidic microenvironment specifically inducing topological transformation from nanoparticles to organelle‐like hydrogel architecture in living cells is reported.