| Affiliation: | 1. Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350 P. R. China These authors contributed equally to this work.;2. Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350 P. R. China;3. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350 P. R. China;4. School of Chemical Engineering and Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW, 2052 Australia;5. Department of Biological &Environmental Engineering, Cornell University, Ithaca, NY, 14853 USA;6. State Key Laboratory of Chemo/Biosensing & Chemometrics, College of Chemistry & Chemical Engineering, Hunan University, Changsha, 410082 P. R. China |
| Abstract: | 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. |
