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Cell-like structures responsive to magnetic fields: a lead to new therapeutics?

Researchers at Imperial College London in the UK have taken a step towards their goal of developing fully programmable cell-like systems that could be used for therapeutic and other applications. They designed cell-like devices whose biochemical processes are activated and modulated by magnetic fields. This is a promising technology that the team now hopes to develop further for biomedical applications. Their results were published in the Journal of the American Chemical Society (JACS) in May 2024.

Yuval Elani, Associate Professor at Imperial College, and his colleagues believe in the transformative potential of synthetic cells, particularly in the field of biomedicine. But for this to happen, synthetic cell technologies will have to be fully controllable.

“What makes a cell therapy effective? Ideally, it should be activated at the right time, only at the target site and produce just enough of the desired therapeutic to eradicate the disease without being toxic to the surrounding tissue,” said Yuval. “So the location, timing and extent of activation of your system is what you need to control to consider therapeutic applications of synthetic cells. External stimuli for this type of control are therefore very interesting for researchers, such as myself, thinking about real-world applications for synthetic cells.”

The potential of magnetic fields to activate processes in synthetic cells

Various studies have been carried out to design cell-like systems that react to stimuli such as light or temperature in order to control the activation of biochemical processes within them. However other stimuli exist and have been used in other areas of research.  This is the case with magnetic fields, whose non-invasive, tissue-penetrating properties make them particularly appealing for medical applications.

“Magnetic fields have been used for many years in imaging and increasingly for therapeutic applications. Given the multiple advantages of magnetic fields, we wondered whether we could design synthetic cells whose biochemical processes could be activated and modulated by magnetic fields.”

The project was carried out entirely by PhD student Karen Zhu from Yuval Elani’s group, with the support of Imperial College researchers Ignacio Gispert Contamina, Laura Barter and two members of the SynCellEU community, Oscar Ces and James Hindley.

Synthetic components to make their systems sensitive to magnetic fields

They began by designing organelles (i.e. subcellular structures) that react to magnetic fields, achieved by incorporating non-biological components. “This is the advantage of using synthetic cells rather than living cells. Living cells do not interact naturally with magnetic fields and it is very difficult to reengineer them so that they respond to magnetic stimuli. Since synthetic cells are not living, it is possible to use both biological building blocks and complete synthetic building blocks in their design. In our case, we used synthetic magnetic nanoparticles to build the organelles.”

The organelles were then inserted into giant unilamellar vesicles (GUVs) and activated by magnetic stimulation, triggering an enzymatic reaction and the synthesis of fluorescent products in the GUV. They were able to control the timing and extent of activation, and hence its modulation, using different magnetic field strengths.

Next steps: permeability, biological context, and motility and bioelectronic systems

The team now wants to determine whether this device can be used in therapeutic applications.

“The next stage of the project is to selectively release what is produced by the GUVs into the environment. For the moment, our systems are impermeable, so the products remain inside. Once we have reached the production-release phase, the next important step will be to introduce these systems into a tissue model, to ensure that they are stable, compatible with the tissue and do not interfere negatively with it,” said Yuval.

Earlier Yuval mentioned that an effective therapeutic product should only activate at the target site. Magnetic fields are also used to move objects. In a third phase, Elani and his colleagues would like to exploit the dual potential of magnetic fields: can they move their cell-like systems to the desired location and, once there, activate them simply by changing the frequency of the stimuli?

Yuval concluded: “I think the next big step in our field will be to use abiotic building blocks to give synthetic cells functionality that we can’t easily give to living cells. For example, synthetic cells have great potential for bridging the gap between computing and biology. By designing synthetic cells controlled by electronics, we could provide an interface between computing and biology. Our field should definitely aim for this.”