A team at the University of Stuttgart has developed a programmable DNA origami nanosyringe that can mechanically transport molecules across synthetic cell membranes. The device, described in Nature Nanotechnology, is designed to anchor itself to a lipid membrane, drive a nanoscale needle through the barrier, deliver molecular cargo, and then retract without permanently damaging the membrane. The advance could provide synthetic biology with a new way to control when and where biochemical reactions begin inside artificial cells.
Membrane transport is one of biology’s most fundamental operations. Small molecules can sometimes cross membranes by diffusion, but many biological tasks require active, precisely directed movement. Nature has evolved molecular machines that use mechanical forces to pierce membranes or inject cargo into target cells. Certain bacteria, for example, deploy contractile injection systems that function like microscopic spring-loaded devices. At a very different scale, intracytoplasmic sperm injection introduces a sperm cell directly into an egg using a fine needle. The Stuttgart researchers adapted this general principle—mechanical penetration followed by controlled delivery—to the nanoscale using DNA molecules.
The nanosyringe is built from DNA origami, a technique in which long DNA strands are folded into predetermined three-dimensional shapes with the help of shorter “staple” strands. Although DNA is best known for storing genetic information, its predictable base-pairing rules also make it a versatile construction material. By designing specific sequences and geometries, researchers can create molecular structures that act as hinges, clamps, channels and moving components. In this case, the DNA framework forms a membrane-anchoring base and a mobile needle linked by a reversible sliding mechanism.
Once attached to a lipid membrane, the device can be activated through DNA strand-displacement reactions. In these reactions, a new DNA strand binds to an exposed sequence and displaces another strand from a double helix. The researchers used this programmable chemistry to drive the nanosyringe’s needle forward and backward. The resulting motion is not a random fluctuation but a controlled mechanical cycle: the needle advances through the membrane, carries or exposes molecular cargo on the other side, and later retracts. This gives the system temporal control over transport that passive diffusion through pores cannot provide.
The work was demonstrated in synthetic cell-like compartments surrounded by lipid membranes. These membrane-bound systems are widely used in synthetic biology because they reproduce selected features of living cells without the complexity of a complete organism. By operating at the boundary between the outside environment and the compartment interior, the nanosyringe can introduce functional molecules precisely where they are needed. Its reversible action is particularly important because many artificial delivery systems disrupt membranes permanently, causing leakage and making it difficult to control subsequent reactions.
The researchers showed that the nanosyringe could do more than move molecular material from one side of a membrane to the other. It also acted as a programmable trigger for biochemical activity inside synthetic cells. In one demonstration, the device initiated DNA hybridization chain reactions at the membrane. These reactions use a series of designed DNA strands that assemble into extended structures once a starter sequence is introduced. Because the starter can be delivered at a selected time and location, the nanosyringe offers a way to spatially organize molecular assembly rather than allowing it to occur uniformly throughout a compartment.
The platform was also used to activate RNA transcription. The researchers transported promoter activators into membrane-bound compartments, where the molecules could engage the transcription machinery and initiate the production of RNA. In another experiment, the device delivered catalytic DNAzymes—synthetic DNA molecules capable of promoting specific chemical reactions. The DNAzymes selectively cleaved RNA substrates inside the compartments, demonstrating that mechanically controlled membrane entry can regulate downstream molecular functions. Together, these tests show that the nanosyringe can serve as an interface for programming reactions, not merely as a passive cargo carrier.
The technology introduces a mechanical dimension to programmable DNA nanotechnology, which has traditionally relied heavily on molecular recognition, hybridization and chemical binding. Instead of responding only to the presence of a target sequence, the nanosyringe physically interacts with a membrane and changes its position through designed motion. Such behavior could eventually allow networks of DNA devices to communicate with synthetic cells, coordinate the release of proteins or nucleic acids, and respond to changing biochemical conditions. The system may also help researchers build artificial cells whose internal reactions can be started, stopped or localized from outside.
Several challenges remain before the concept can be translated into practical biomedical applications. Future versions will need to transport larger and more diverse cargos, including proteins, therapeutic nucleic acids and molecular sensors. Researchers will also need to improve the device’s efficiency, stability and selectivity in complex biological fluids, where membranes contain many different lipids and proteins. The precision demonstrated in synthetic compartments may be difficult to reproduce in living cells, whose surfaces are dynamic and actively remodeled. Nevertheless, the reversible nanoscale penetration mechanism establishes a new design strategy for engineered biointerfaces.
The Stuttgart study presents the DNA origami nanosyringe as a compact molecular machine capable of combining anchoring, mechanical motion, membrane penetration and biochemical control. By merging the programmability of DNA chemistry with the direct force of a nanoscale actuator, the device offers a new way to communicate with synthetic cells and potentially biological systems. The broader significance lies in treating molecular transport as an active, addressable process: cargo does not simply diffuse across a barrier, but is delivered through a programmed mechanical event. That approach could help transform artificial cells from passive chemical containers into dynamic systems capable of controlled interaction with their surroundings.
Subject of Research: A programmable DNA origami nanosyringe for mechanically controlled molecular transport across synthetic cell membranes.
Article Title: Programming membrane transport
News Publication Date: 11-Aug-2026
Web References: https://www.nature.com/articles/s41565-026-02249-3
References: DOI: 10.1038/s41565-026-02249-3; Nature Nanotechnology
Image Credits: Copyright: University of Stuttgart, 2nd Physics
Keywords: DNA origami, nanosyringe, nanotechnology, synthetic cells, membrane transport, molecular machines, synthetic biology, DNA nanotechnology, molecular therapeutics, engineered biointerfaces
