Macromolecular crowding could help build artificial cell systems

Macromolecular crowding can be a valuable design tool for creating and organizing artificial DNA droplets, according to a new study from Science Tokyo. Researchers used DNA nanostars and polymeric crowding agents to mimic the crowded cellular environment. The findings suggest that this crowded environment, known as macromolecular crowding, can influence the formation, stability and organization of these droplets, which could support the development of programmable artificial cell systems.

DNA molecules often cluster into densely packed areas called biomolecular condensates, which regulate various cellular processes. However, the cellular interior is also densely packed with other large molecules that can impact the properties of these condensates. To investigate this, Japanese researchers from the Institute of Science Tokyo used synthetic Y-shaped branched DNA nanostructures known as DNA nanostars.

These structures self-assemble into liquid-like droplets and were used to study the effects of crowding agents on their formation, stability and organization. By creating a molecularly crowded environment with polymeric crowding agents, the scientists found that these agents promoted droplet formation at higher temperatures and helped the droplets remain stable.

Among the crowding agents tested, polyethylene glycol (PEG) demonstrated the most significant effect. While PEG can promote droplet formation, it requires sticky-end interactions with the DNA nanostars to work effectively. The researchers demonstrated that by controlling the concentration of PEG, the ratio of different nanostar types, and the salt concentration, they could control how the droplets interacted and were organized into specific patterns, ranging from alternating structures to more complex multicomponent structures.

This study reveals that macromolecular crowding is not just a characteristic of the cellular environment but can also serve as a powerful design parameter for engineering artificial DNA condensates. By leveraging this principle, researchers could develop synthetic biomolecular systems with controlled structures and functions, potentially leading to advancements in artificial cell tissues, molecular communication networks, molecular computing systems, and programmable micromachines.