A novel reaction-diffusion architecture for engineering self-organized patterns in mammalian cells

The ‘spotLight’ featured here is part of our ‘preprints by preLighters’ series, where we highlight exciting preprints authored by members of the preLights community.

Transcript:

Did you ever wonder how the leopard got its spots? Or how the zebra got its stripes? Wonder no more! We understand the process of pattern formation so well that we can recreate it in a dish.

70 years ago, mathematician Alan Turing developed a theory on how biological patterns could self-organise using morphogens that just do two things. They react with each other and they move in space through diffusion. If you simulate these simple networks on a computer, you can generate patterns from scratch.

Now biologists believe that reaction-diffusion does not only underlie the formation of skin coat patterning but also other structures during embryonic developments including hair follicles fingerprints and the development of five fingers.

The problem with biology is that it’s extremely complex. Every process involves hundreds if not thousands of genes. So how can we truly prove that simple reaction diffusion circuits are sufficient to generate self-organised patterns?

This is where synthetic biology kicks in. We can understand something by reconstructing it. Inspired by reaction-diffusion theory, we designed simple two component synthetic circuits and demonstrated that indeed they can induce the formation of self-organised patterns in mammalian cells without any additional interactions.

Now we did this with a twist. In classical reaction-diffusion circuits, you need an activator that diffuses slowly and an inhibitor that diffuses faster. But differential diffusion is not an easy thing to engineer. So to bypass this requirement, we designed our activator so that it propagates through cell-cell contacts. rather than diffusion. And we show that theoretically this substitution still allows for efficient self-organised patterning.

Now because these synthetic circuits are compact and modular, we can use them as building blocks towards constructing circuits that can control the self-organisation of more complex multi-coloured patterns such as those shown here.

More broadly, I believe that by learning to engineer biology at the multicellular scale, we’re inching closer towards being able to control and build custom tissues in a dish.

Our findings suggest that even in the messy context of living cells which move and proliferate, the mathematical theory that Turing developed still holds. On the other hand, one limitation of the patterns that we could generate was that they were not perfectly regular. So whether simple two component circuits are really sufficient to control the formation of periodic patterns in the context of living cells remains to be investigated.

We posted our work on bioRxiv as a preprint. This means that you can read it and download it for free. And if you want to know more, feel free to follow me on social media or reach out.

spotLight recorded by: Benjamin Swedlund, postdoctoral researcher at University of Southern California, Los Angeles, USA & Aman Ahmed, PhD student at University of Southern California, Los Angeles, USA

spotLight edited by: Reinier Prosee, Preprints Community Manager, The Company of Biologists, Cambridge, UK

Tags: developmental biology, pattern formation, self-organisation, synthetic biology, tissue engineering, turing patterns