# Semi‐Independent Control of Stability and Mobility in DNA Condensates

## TL;DR

Researchers developed a method to adjust the stability and fluidity of DNA droplets separately, which is important for creating artificial cells and molecular robots.

## Contribution

A strategy to semi-independently control thermal stability and dynamics in DNA droplets using variable-length sticky ends.

## Key findings

- Extending variable sticky ends increased the phase-separation temperature without reducing droplet dynamics in a specific range.
- Droplet fluidity was maintained when the melting temperature of variable sticky ends remained below the phase-separation temperature.
- Excessively long sticky ends inhibited droplet dynamics due to stable polymerization.

## Abstract

Liquid‐like biomolecular condensates possess unique physical properties that are essential for cellular functions and artificial cell engineering. However, increasing the thermal stability of these condensates typically reduces their liquid‐like dynamics. Here, we report a strategy to semi‐independently control the thermal stability and dynamic properties of DNA droplets formed from six‐branched DNA nanostructures (S‐motifs). We designed S‐motifs containing four fixed sticky ends (SEs) composed of 4 nucleotides (nt) and two variable‐length SEs of 0–20 nt in length. Extending the length of the two variable SEs increased the phase‐separation temperature (T
p) of the droplets. Within a specific range (4–12 nt), where the melting temperature (T
m) of the variable SEs remained below T
p, the droplets maintained their fusion dynamics and internal mobility despite increased thermal stability. In contrast, when the variable SE length was 16–20 nt and T
m exceeded T
p, the dynamic behaviors were inhibited because of stable polymerization. These findings demonstrate that the partial modification of the SE binding strength enables the tuning of thermal stability without sacrificing liquid fluidity, providing a valuable design principle for developing functional DNA‐based artificial cells and molecular robots.

This article reports a strategy to semi‐independently control thermal stability and dynamics of DNA droplets composed of branched DNA nanostructures. By extending two variable sticky ends (SEs) while maintaining the others, the thermal stability increased without significantly reducing liquid‐like fusion or internal mobility. This demonstrates that partial SE modification enables stability tuning without sacrificing droplet fluidity for artificial cell engineering.© 2026 WILEY‐VCH GmbH