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

Abstract

The design of controllable dynamic systems is vital for the construction of organelle-like architectures in living cells,b ut has proven difficult due to the lack of control over defined topological transformation of self-assembled structures.H erein, we report aD NA based dynamic assembly system that achieves lysosomal acidic microenvironment specifically inducing topological transformation from nanoparticles to organelle-like hydrogel architecture in living cells. Designer DNAn anoparticles are constructed from doublestranded DNAwith cytosine-richstick ends (C-monomer) and are internalizedi nto cells through lysosomal pathway.T he lysosomal acidic microenvironment can activate the assembly of DNAm onomers,i nducing transformation from nanoparticles to micro-sized organelle-like hydrogel which could further escape into cytoplasm. We show how the hydrogel regulates cellular behaviors:c ytoskeleton is deformed, cell tentacles are significantly shortened, and cell migration is promoted.

Enzyme-Responsive DNA Condensates

“…31-33 Specifically, synthetic DNA and RNA nanostructures, including branched DNA junctions 34-37 and single-stranded DNA block copolymers, 38,39 have been adopted to construct membrane-less compartments with advanced functionalities. These include the ability to capture and release molecular cargoes, 40,41 host enzymatic reactions, 27,42-44 interface with live cells, 45,46 and undergo structural transformations induced by changes in pH, 47,48 ionic conditions, 49 or light. 40,50 Advances have also been made towards establishing physical and chemical heterogeneity within DNA-based membrane-less compartments, for instance by exploiting reaction-diffusion processes 27 or phase separation.…”