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Updated: Jan 28, 2026

Author Spotlight: Developing Synthetic Cells from Programmable Amphiphilic DNA Nanostructures

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.

ACS Applied Bio Materials

|January 26, 2026

Summary

DNA actively drives liquid-liquid phase separation (LLPS) in cells and synthetic systems. This research explores DNA

Keywords:

DNA droplets DNA hydrogel artificial DNA junctions biomolecular condensates liquid−liquid phase separation synthetic cells

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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.