Presentation Information
[2ASPR-03]Triggered DNA Phase Separation as a Mechanism for Programmable Membrane Interaction in vescles
○Richard J. Archer1 (1. Institute of Science Tokyo (Japan))
Keywords:
DNA Condensates,Vesicles,Stimuli-Responsive
The development of smart biomolecular systems capable of sensing specific molecular cues and autonomously executing functional responses is a key objective in next-generation synthetic biotechnology and drug delivery.
Here, we present a DNA-based, responsive platform in which phase-separated DNA condensates induce controlled destabilization of giant unilamellar esicles, providing a route toward programmable synthetic biointerfaces.
We engineered cholesterol-modified DNA (Chol-DNA) Y-motifs that undergo sequence-specific assembly and liquid–liquid phase separation upon introduction of defined nucleic acid inputs. The resulting DNA condensates interact with giant unilamellar vesicles (GUVs) through cholesterol-mediated membrane insertion, enabling coupling between molecular recognition and membrane mechanics.
Using fluorescence microscopy, we demonstrate that Chol-DNA condensates localize at GUV membranes. By systematically varying the fraction of cholesterol-modified motifs, we identify a threshold behavior: membrane integrity is preserved at low cholesterol content, while high concentrations lead to membrane destabilization and vesicle rupture, accompanied by lipid aggregation. This transition highlights the tunability of DNA–lipid interactions and their capacity to regulate membrane stability.
This system links nucleic acid sensing to a functional output—membrane disruption—suggesting a pathway toward autonomous, DNA-programmed drug delivery systems responsive to disease-associated molecular signals (e.g., miRNA). More broadly, our results establish DNA condensates as versatile, programmable modules for engineering responsive biointerfaces and synthetic cellular systems.
Here, we present a DNA-based, responsive platform in which phase-separated DNA condensates induce controlled destabilization of giant unilamellar esicles, providing a route toward programmable synthetic biointerfaces.
We engineered cholesterol-modified DNA (Chol-DNA) Y-motifs that undergo sequence-specific assembly and liquid–liquid phase separation upon introduction of defined nucleic acid inputs. The resulting DNA condensates interact with giant unilamellar vesicles (GUVs) through cholesterol-mediated membrane insertion, enabling coupling between molecular recognition and membrane mechanics.
Using fluorescence microscopy, we demonstrate that Chol-DNA condensates localize at GUV membranes. By systematically varying the fraction of cholesterol-modified motifs, we identify a threshold behavior: membrane integrity is preserved at low cholesterol content, while high concentrations lead to membrane destabilization and vesicle rupture, accompanied by lipid aggregation. This transition highlights the tunability of DNA–lipid interactions and their capacity to regulate membrane stability.
This system links nucleic acid sensing to a functional output—membrane disruption—suggesting a pathway toward autonomous, DNA-programmed drug delivery systems responsive to disease-associated molecular signals (e.g., miRNA). More broadly, our results establish DNA condensates as versatile, programmable modules for engineering responsive biointerfaces and synthetic cellular systems.
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