Synthetic Cells: what are they and why make them?

On Monday 10 November, the EngBio IRC hosted our latest EngBio Forum. We were delighted to welcome keynote speakers Prof Andreas Walther and Dr Claudia Contini. The speakers shared some of the latest developments in synthetic cell research, as well as some interesting insights into potential new applications for this growing field.

So what are synthetic cells? How are they made? What can they do? And how can we make use of them? Below I share a brief overview of the field and some of the exciting work shared by our speakers last month.

What are Synthetic Cells?

What I cannot create, I do not understand” - Richard Feynman

Dr Contini’s talk started with this timeless quote that excellently summarises the interests of many in the synthetic cell field - to gain greater understanding of how cells work by building them from the bottom up. As we start to build we find things that don’t work, and this reveals the gaps in our knowledge. We can then strive to unravel these mysteries and use the findings to build a better prototype next time.

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However, synthetic cell research is not just about recreating current biological systems. It is also, as Claudia put it, about “taking biological principles and translating them for use in bio-inspired design”. In other words, we can use synthetic cells to build new and exciting biology that isn’t possible in existing systems.

How are synthetic cells made?

As Dr Contini highlighted, the first step in creating synthetic cells is compartmentalisation - creating an enclosed environment to mimic a cell's separation from the outside world. Most often this is achieved by using lipids, and other polymers, to create vesicles. Both Claudia and Andreas use this approach in their work, but there are also other methods used in the field.

For example, Prof Walther’s work also explores the use of DNA-based cells, which use DNA structures to encapsulate the synthetic cell. Excitingly, the Walther Lab’s recent work has developed DNA-based cells that not only form an outer capsule, but also contain an internal DNA-based structure, similar to a cytoskeleton.¹ These DNA cytoskeletons provide exciting new opportunities to control signalling within synthetic cells.

What can synthetic cells do?

Both speakers are working to push the boundaries of what synthetic cells can do, and to establish new and useful capabilities and behaviours in these systems. Some of the most intriguing works shared by Prof Walther and Dr Contini included:

• Signal Processing
  Andreas shared a system that allows signals to pass across the synthetic cell membrane. This offers exciting possibilities for synthetic cells to be able to recognise and process signals from their environment, as well as established internal signal processing.²
   
• Formation of Prototissues
  The Walther lab is also working towards the formation of multicellular systems using synthetic cells. These prototissues aim to mimic the behaviour of living tissues, such as communications, collective behaviour and homeostasis.³
   
• Motility
  Claudia discussed her work on inducing motility in synthetic cells. Her motile cells are able undergo chemotaxis - moving towards or away from chemical signals. This behaviour paves the way for targeting synthetic cells, for example in drug delivery.^4,5
   
• Biohybrids
  Dr Contini also described her experiments with biohybrid systems, combining synthetic cell and bacterial systems to further expand the possibilities. Her lab has developed heat-sensitive synthetic cells which can expand in order to trap cargo such as small molecules and bacteria.⁶ They are also working on bacteria-hydrogel systems which can respond to magnetic stimuli.⁷

How can we use synthetic cells?

The applications of synthetic cells are myriad, from bioproduction and carbon capture to diagnostics and therapeutics. Both speakers are working to apply their research to tackle real-worlds problems. In Prof Walther’s case, his lab has developed a system which recognises high levels of ATP - for example in tumours - to deliver and release cargo - for example chemotherapies. They hope that this work will enable targeted drug delivery and gene therapies that can adapt their dosing based on ATP levels.⁸ In Dr Contini’s lab they are working to adapt their biohybrids into biocompatible drug delivery systems and biosensors.⁷

It was a privilege to hear from two such excellent speakers, and to learn more about their work. I came away with the feeling that the possibilities for the future of synthetic cell research are endless! As Claudia said during her introduction, engineering biology from the bottom up allows to us gain a better understanding of living systems, but also affords us the opportunity to build new systems which could help us tackle some of society's most pressing problems. I look forward to seeing future work from the labs of our two excellent speakers, and wonder where the field will go next…