A Modular, Dynamic, DNA-Based Platform for Regulating Cargo Distribution and Transport between Lipid Domains

Area of Science:

• Synthetic Biology
• Biomaterials Science
• Chemical Engineering

Background:

• Cell membranes utilize phase-separated lipid domains to compartmentalize cellular machinery, enabling essential functions like signaling and transport.
• Bottom-up synthetic biology seeks to engineer artificial cellular systems with life-like functionalities, requiring precise control over molecular organization within membranes.

Purpose of the Study:

• To develop a modular strategy for programming the spatial distribution of amphiphilic DNA nanostructures within coexisting lipid domains.
• To demonstrate the ability to control nanostructure partitioning by tuning hydrophobic interactions, size, and topology.
• To engineer a DNA-based system capable of ligand-induced cargo transport between lipid domains.

Main Methods:

• Designing amphiphilic DNA nanostructures with varying hydrophobic anchors to exploit differential partitioning in distinct lipid phases.
• Modulating nanostructure lateral distribution through rational combination of hydrophobic moieties, size, and topological variations.
• Utilizing a bioinspired DNA architecture that undergoes ligand-induced reconfiguration for dynamic cargo transport.

Main Results:

• Demonstrated successful programming of DNA nanostructure partitioning in coexisting lipid domains.
• Showcased modulation of nanostructure distribution by altering hydrophobic anchor composition and nanostructure characteristics.
• Validated a DNA-based system for ligand-inducible, inter-domain cargo transport via nanostructure redistribution.

Conclusions:

• The modular approach enables precise control over the spatial organization of synthetic components within artificial cellular environments.
• This strategy facilitates the development of advanced biomimetic platforms for sensing, signal transduction, and communication in synthetic cells.
• The findings represent a significant step towards engineering sophisticated functionalities in bottom-up artificial cellular systems.