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Updated: Jan 28, 2026

Author Spotlight: Developing Synthetic Cells from Programmable Amphiphilic DNA Nanostructures
Published on: May 31, 2024
DNA-Driven Liquid-Liquid Phase Separation from Cellular Condensates to Programmable Synthetic Systems.
Sanjay Kosara1, Abhijit Biswas1, Amit K Yadav1
1Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Near Palaj, Gandhinagar, Gujarat 382055, India.
DNA actively drives liquid-liquid phase separation (LLPS) in cells and synthetic systems. This research explores DNA
Area of Science:
- Biophysics
- Molecular Biology
- Materials Science
Background:
- Liquid-liquid phase separation (LLPS) creates membraneless condensates regulating cellular functions.
- While proteins and RNA were primary focus, DNA is now recognized as an active LLPS driver.
- DNA condensates are crucial for nuclear processes like chromatin organization and gene regulation.
Purpose of the Study:
- To synthesize current understanding of DNA-mediated LLPS in biological and synthetic contexts.
- To highlight underappreciated aspects of DNA's role in phase separation.
- To bridge fundamental biophysics with engineering principles for synthetic DNA systems.
Main Methods:
- Review and synthesis of existing research on DNA-mediated LLPS.
- Emphasis on five key underappreciated topics: DNA's driving role, reversible aggregation, non-Fickian transport, mechanical characterization, and multiscale complexity.
- Highlighting advanced single-molecule technologies like optical tweezers and scanning probe microscopy.
Main Results:
- DNA actively drives LLPS via charge and topology, distinct from passive roles.
- DNA aggregation can be reversible, differing from irreversible protein misfolding.
- Non-Fickian transport, including ballistic wave diffusion, occurs in DNA condensates.
- Single-molecule techniques reveal state-dependent material properties of DNA condensates.
- Cellular DNA condensation involves multiscale complexity influenced by topology and hierarchy.
Conclusions:
- DNA is a fundamental driver of phase separation in both natural and synthetic systems.
- Understanding DNA-mediated LLPS offers insights into cellular processes and enables new biomaterials.
- This integrated perspective provides a framework for developing therapeutic and biotechnological applications.

