Synthetic Cells: Magnetic On-Off Control Breakthrough!

Can we create synthetic cells? Can we turn them ON and OFF?

Answers to these and more questions here, today!

Synthetic Cells Switches

Synthetic cells are the holy grail of synthetic biology (probably!).

We are still far from building fully artificial cells, but we’re learning how to mimic natural systems. And these artificial constructs are carving out a role as powerful tools for drug delivery, biosensing, and biomedicine in general.

Most synthetic cells today are lipid membranes packed with DNA and proteins to create a cell-free protein synthesis (CFPS) system. But they can also include non-biological components to add new functions and transform them into powerful chemical microfactories!

But the road there is still long.

One of the biggest problems is the control of their activity. How do you switch them ON or OFF when you want? This is kind of important for any application, medical or otherwise! The main strategies so far:

• Small molecules (easy to use, not really selective)

• UV light (precise, but struggles to penetrate tissues)

Both have limits. If you want to control synthetic cells inside living organisms, you need something better!

Magnetic Fields for the Win

What if the answer was magnetic fields?

Alternating magnetic fields (AMFs) can travel deep inside tissues (over 10 cm!). They’re safe, already used in medicine (think MRI), and don’t mess with biology on their own.

But magnetic fields alone can’t do much. They need something to work with.

Superparamagnetic Nanoparticles: More Than Just a Cool Name

Today’s paper proves that DNA can be combined with pretty much anything, even magnets. The authors built spherical nucleic acids (SNAs, nanoparticles densely coated with DNA) that can switch synthetic cells ON, remotely and on demand!

The team started with superparamagnetic iron oxide nanoparticles, with a cool name and interesting properties.

These biocompatible nanoparticles (they are inside iron supplements and contrast agents for MRI) can release heat inside an AMF. This is called magnetic hyperthermia, and it’s a clinically approved treatment! It can kill tumour cells and spare healthy cells, less affected by higher temperatures.

The team used the magnetic nanoparticles as a core, coating them in silica and conjugating them with double-stranded DNA to create the SNAs.

And here is the trick. This dsDNA contains a T7 promoter sequence. When the magnetic hyperthermia warms up the core of the SNA, the released heat denatures the DNA. The T7 promoter will then bind to an “incomplete” DNA template, starting protein production! Super smart and elegant.

Synthetic Fluorescent Cells

To turn their magnetic SNAs into real synthetic cells, the authors encapsulated them into giant unilamellar vesicles (GUVs). These lipid-based microstructures are often used as biomimetic models for the cell membrane.

Together with the SNAs, the team inserted into the GUVs the CFPS machinery and an inactive DNA template, with a sequence complementary to the T7 promoter on the SNAs. When the promoter is released, the DNA template is read, and the cells start glowing with mNeonGreen fluorescence!

At least, this is the plan. Did it work?

Using fluorescent microscopy, they tracked the production of the fluorescent protein inside the GUVs. And the results were great:

• The transcription in the OFF state was low, at 6% of the active template

• After activating the AMF, transcription recovered to around 95-100% of the fully intact template!

• The AMF worked to activate samples behind opaque barriers (mimicking tissue), where light or small molecules would fail.

Functional Output: Protein-Mediated Cargo Release

The team demonstrated the versatility of the system by applying it to a different application: the release of cargo from the GUVs.

This time, they loaded the GUVs with even more components:

• CFPS machinery (ribosomes, T7 RNAP, amino acids, cofactors)

• Inactive DNA template

• SNA promoter carriers

• A fluorescent sugar analog (2-NBDG)

• The DNA template for the pore-forming protein α-hemolysin (α-HL)

The plan was for the fluorescent 2-NBDG to act as a cargo. After the AMF activated protein expression, α-HL would create pores on the GUVs, and 2-NBDG would leak out. This would be amazing for targeted drug delivery!

And it worked, with the magnetically activated GUVs showing a significant reduction in fluorescence!

Future Directions

Such a cool study! An elegant and smart approach. I love these papers that use exotic (for me!) materials’ properties to fix real-world problems.

And this study could have big implications. The new method:

• Provides robust, leak-free OFF states

• Enables deep-tissue activation with existing medical AMF devices (and with safe frequencies)

• Demonstrates both gene expression control and on-demand release!

So, it could be the foundation for a new generation of magnetically controlled, smart therapeutic synthetic cells!

I enjoyed this paper, and it was written clearly, which made my life so much easier! Get all the details here.

If you made it this far, thank you! What do you think of this new method? Or of synthetic cells in general? Reply and let me know!

More Room:

• Programming DNA Sensing: Nucleic acids are important to detect, and scientists are always on the hunt for better ways to do it. This study presents a framework nucleic acid (FNA)-programmed strategy to create densely monodispersed nucleic acid recognition interfaces. By using tetrahedral DNA nanostructures to anchor single-stranded DNA probes, the authors achieved uniform probe orientation and spacing, overcoming limitations of conventional probe interfaces. This design enabled faster hybridization kinetics, higher efficiency, and significantly improved signal-to-noise ratios: up to 12.7-fold better than conventional probe designs!

• Patterns, Behaviours, and DNA: Modifying the DNA of bacteria is a common thing. Putting DNA on the outside of them? Not as much. This study demonstrates the use of functional DNA as programmable surface receptors to control microbial interactions and assemblies. By modifying diverse microorganisms with DNA, researchers achieved precise spatial organization of bi- and tricomponent communities and enabled stimuli-responsive clustering using aptamers and strand displacement. The approach allows dynamic regulation of behaviors like biofilm formation, antibiotic sensitivity, and quorum sensing, offering a powerful new tool for engineering microbial communities in synthetic biology and medicine.

• Storing Energy in DNA Hydrogels: Photoimmunotherapy combines phototherapy and immunotherapy. Can we also combine it with DNA? This study introduces a smart DNA hydrogel that enables laser-free, on-demand photoimmunotherapy for melanoma. The hydrogel integrates aptamers, CpG oligonucleotides, and energy-storing nanoparticles to selectively trigger phototherapy and immune activation in response to tumor markers. In mouse models, it achieved a 73.3% tumor inhibition rate, highlighting DNA hydrogels as a promising platform for precise, marker-responsive cancer treatment.

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