Artificial cells are the holy grail of synthetic biology.
Can we create artificial cells without using any protein? Of course! DNA nanotech is your friend there.
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DNA Builds Reactors
Researchers created artificial cells with controlled transport signalling by combining synthetic vesicles and DNA nanopores.
Cells as Microreactors
Cells are basically tiny chemical reactors.
Inside their little membrane, they organize thousands of biochemical reactions at the same time! And membranes are not just sitting there. They actively regulate permeability! They decide who can enter and who stays out.
Membrane proteins do most of the work. They control permeability through pores, pumps, and channels, and let cells sense their environment and react dynamically!
I’ll give you 2 examples:
MscL → senses high membrane tension in bacteria and opens to prevent the cell from exploding.
BAX → forms pores in mitochondria during cellular stress, releasing cytochrome c and activating programmed cell death.
Different outcomes, same biological idea! Signaling pathways and membrane proteins coordinate changes in membrane permeability, with life-or-death consequences!
Towards Synthetic Cells
So, naturally, scientists wanted to make their own versions!
Creating synthetic cells is one of the biggest goals of synthetic biology. We could create custom drug factories, artificial tissues, smart biosensors, and more! But we’re not there yet.
Today, the most popular platform for synthetic cells is giant unilamellar vesicles (GUVs). Spherical compartments surrounded by a single lipid bilayer, they’re perfect to mimic cell membranes:
Same size as cells (1-100 μm)
Customizable membrane composition
Simple and controllable
Scientists have already inserted all kinds of transporters into GUVs: protein pores, ion channels, transport proteins. But natural proteins are not very programmable. Can we do better?
DNA Nanotech Enters the Chat
Yes, with DNA nanotechnology!
Researchers now use DNA not as a genetic material, but as a construction material to build nanoscale structures with precise geometry and programmable behaviour. And with DNA nanopores, you can replicate cell transporters!
DNA nanopores are synthetic pores made entirely from DNA. Inside a GUV, they behave like membrane channels, but unlike proteins, you can redesign almost everything: pore diameter, shape, geometry!
And you can make pores responsive to:
DNA strands
Protein
Light
Voltage!
You get programmable membrane transport.
The catch?
Most DNA nanopores have only been used in isolation: one pore type on one GUV. Not very cell-like! Cells use proteins to create complex, interacting pathways to modulate membrane dynamics.
Double-Necked Synthetic Cells
Today’s paper tackles that problem!
The authors built a double-necked synthetic cell microreactor (DCM). The idea is to combine GUVs with two different DNA nanopores to create a synthetic cell capable of signalling-like behaviour!
The DNA pores are not just passive holes in a membrane: they’re interacting, dynamic machines! The authors use them to tune the delivery of materials inside the GUVs and create micro-reactors for confined reactions.
Double the Pores, Double the Fun
The DCM consists of 3 parts:
A GUV as the reaction vessel.
Light-responsive small pores (SPs)
These are barrel-shaped structures just 12.5 nm in height and 2 nm in diameter. They have a light-responsive lid strand.
SPs are synthesized closed → UV-light opens them → Visible light closes them again! When open, SPs allow small cargo to move across the membrane: ions, fluorophores, and sucrose!Self-arranged large pores (LPs)
Formed by DNA origami rafts that change shape from a square state (s-DR) to an elongated rectangle state (e-DR) when you add unlocking strands. The shape change creates membrane deformation, and when the membrane recovers, re-sealable pores form. LPs are 7x bigger than SPs (15 nm vs 2 nm!) and they can transport much larger cargo: GFP, dextran, and single-stranded DNA (ssDNA).
Pore-Pore Signaling Through Membrane Dynamics
The key central idea is that pores interact in a synthetic signalling pathway.
In cells, signalling pathways are networks of chemical reactions that let them perform their functions. The researchers wanted to recreate something similar: a transport system where one membrane component helps trigger the other via membrane dynamics.
Here’s how it works:
Unlocking strands convert s-DRs → e-DRs
The e-DRs deform the GUV membrane
UV light opens SPs
Ions and sucrose enter the membrane, and it recovers its shape
During recovery, LPs form
One pore system indirectly regulates the other. SPs and LPs are interdependent, not independent.
DCM can be in 4 states:
SP1-LP1 → both open → small and big cargoes enter
SP0-LP0 → SP closed, LP open → small and big cargoes enter from LPs
SP1-LP0 → SP open, LP closed → only small cargoes
SP0-LP0 → both closed → nothing enters!
Bringing Real Applications Inside GUVs
The team didn’t stop at building the system. They used it in 4 real reactions!
Application 1: GOx-myoglobin enzyme cascade
The DCM is used to deliver the different components of a glucose oxidase-myoglobin (GOx-Mb) cascade:
GOx is encapsulated in the GUV
Amplex Red is added outside and can enter through the membrane
Myoglobin is delivered via LPs (that are then closed)
Glucose enters via SPs
The result? Amplex Red turns fluorescent after glucose oxidation! But the point is not that the enzymes work. It’s that DCM can deliver reagents in the right order!
Application 2: actin polymerization and bundling
What do you need to make a cell? Of course, a cytoskeleton.
And with DCM, you can make one:
G-actin is transported via LPs
ATP enters using both pores
G-actin binds to ATP and polymerizes into F-actin
Fascin enters through LPs, bundling the filaments into dense networks!
This is pretty much how cytoskeletal assembly works in real cells!
Application 3: cell-free Spinach RNA transcription
Third, the authors bring cell-free transcription to DCM:
T7 is pre-encapsulated in the GUV
The DNA template enters via LPs
The rest of the transcription mixes through both pores
The pores are then closed, and transcription happens. Once it’s done, the pores are opened again, so that the small molecule DFHBI can enter, bind to the Spinach RNA, and produce fluorescence!
Application 4: 3D DNA crystal synthesis
Lastly, the coolest materials science result!
The team synthesized 3D DNA crystals inside DCMs, in a world-first. Generally, DNA crystals are produced in solution with inconsistent results. Here? You can stage the steps:
DNA triangle motifs enter through LPs
LPs are sealed
Mg2+ is gradually added through Sps
You wait 2 days, and you get crystals!
The result? Over 70% of DCM systems have a single crystal → the confinement suppresses multinucleation, leading to a more consistent synthesis.
Conclusions: DNA Cells, Coming Soon
An amazing paper!
The DCM system is a first step toward synthetic cells with coordinated membrane signalling. And in the future, there could be new versions:
More pore types
Integrate protein pores
hybrid synthetic-biological systems
The final goal is to create microfactories, and I think that’s just so cool!
Some limitations of DCM to keep in mind:
Molecular selectivity is still broad
There’s still a lot of manual labour to create the components
The pores are still basic, only recognizing based on size, pretty much
So, yeah, we need more DNA pores! A cool read, go here and get all the details! They have very nice images.
If you made it this far, thank you! What do you think of DNA nanopores? Do you think they have a place in synthetic biology? Reply and let me know!
P.S: Know someone interested in DNA nanotech and SynBio? Share it with them!
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More Room:
Bridging RNA and DNA Nanotech: DNA and RNA nanotech are not really in competition, but what if they became even more compatible? The authors of this paper study how identical RNA and DNA sequences can assemble into different nanostructures. Using an RNA square model, they show that gradually replacing RNA nucleotides with DNA causes the structure to shift from squares to triangles, revealing different self-assembly behaviors between RNA and DNA. Simulations and experiments further show that tuning motif flexibility can produce multiple shapes, offering insights into structural transitions between RNA and DNA nanostructures.
DNA + Sapphire = Data Storage: There is more need than ever for data storage! Can DNA help? This paper develops a DNA-based data storage system that uses nanostructured DNA and low-noise solid-state nanopores for information readout. Data are encoded into DNA four-helix bundles and decoded with high accuracy using machine learning, achieving about 93% classification accuracy. The work highlights the potential of combining DNA nanotechnology and nanopore sensing for secure, high-density data storage.
Programming DNA 101: It’s good to go back to the basics! This perspective discusses how DNA sequence information can be used to program material properties across much larger scales, from nanostructures to complex networks. It highlights how simulations, experiments, and machine learning can be combined to predict and design DNA-based materials with tunable mechanical and functional behaviors. The authors also outline future applications in biomimetic materials, smart biomaterials, and molecular information processing.