A programmable DNA origami nanosyringe for directed membrane translocation

Area of Science:

• Nanotechnology
• Biophysics
• Synthetic Biology

Background:

• Bacterial contractile injection systems serve as models for membrane penetration and molecular cargo delivery.
• Replicating these complex functions in synthetic nanoscale systems presents significant challenges, particularly in integrating structural organization with dynamic actuation, reversibility, and spatiotemporal control.

Purpose of the Study:

• To engineer a synthetic nanoscale system capable of programmable membrane translocation.
• To develop a DNA origami nanosyringe that mimics bacterial injection systems for controlled cargo delivery and biochemical regulation.

Main Methods:

• Fabrication of a DNA origami nanosyringe composed of two DNA origami bundles crosslinked by a gold nanoparticle.
• Functionalization of one bundle as a membrane-anchoring base and the other as a DNA fuel-driven sliding needle.
• Utilizing DNA fuel to actuate the needle for membrane penetration and subsequent retraction for membrane resealing.

Main Results:

• The DNA origami nanosyringe successfully binds to lipid bilayers and vesicles.
• Actuation drives needle penetration in ~14-nm steps, enabling cargo delivery into lipid-bounded compartments.
• Demonstrated regulation of biochemical processes, including hybridization chain reactions, RNA transcription, and catalytic RNA cleavage, within cell-sized environments.

Conclusions:

• The developed DNA origami nanosyringe effectively integrates structural organization with dynamic actuation for programmable membrane translocation.
• This synthetic system provides a versatile platform for controlled molecular cargo delivery and regulation of biochemical functions at membrane interfaces.
• The strategy advances the design of dynamic DNA devices operating at biological interfaces, coordinating mechanical action with biochemical outcomes.