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  • Review Article
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Synthetic morphology with agential materials

Nature Reviews Bioengineering volume 1, pages 46–59 (2023)Cite this article

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Abstract

Bioengineering can address many important needs, from transformative biomedicine to environmental remediation. In addition to practical applications, the construction of new living systems will increase our understanding of biology and will nurture emerging intersections between biological and computational sciences. In this Review, we discuss the transition from cell-level synthetic biology to multicellular synthetic morphology. We highlight experimental embryology studies, including organoids and xenobots, that go beyond the familiar, default outcomes of embryogenesis, revealing the plasticity, interoperability and problem-solving capacities of life. In addition to traditional bottom-up engineering of genes and proteins, design strategies can be pursued based on modelling cell collectives as agential materials, with their own goals, agendas and powers of problem-solving. Such an agential bioengineering approach could transform developmental biology, regenerative medicine and robotics, building on frameworks that include active, computational and agential matter.

Key points

  • Synthetic bioengineering allows the construction of new arrangements of living material.

  • Synthetic morphology aims at creating an ‘anatomical compiler’ that writes DNA instructions based on a specific design goal.

  • Bottom-up bioengineering approaches are limited by knowledge gaps in developmental biology, thus relying on the micromanagement of passive materials.

  • Cells and tissues are effectively manipulated as agential materials, by targeting their pattern memory and homeostatic capabilities.

  • Extending bottom-up approaches by adding empirically and computationally characterized agential materials (cells and tissues) will greatly improve the rational creation and repair of complex morphologies.

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Fig. 1: Competencies of cellular collective intelligence.
Fig. 2: An example of synthetic morphogenesis.
Fig. 3: Optimal engineering strategies depend on the agency level of the material.
Fig. 4: Agential bioengineering.
Fig. 5: Bioelectric interface for organ-level control.
Fig. 6: Xenobot platform for cracking the morphogenetic code.

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Acknowledgements

We thank J. Poirier for assistance with manuscript preparation. M.L. acknowledges support via grant 62212 from the John Templeton Foundation and grant TWCF0606 of the Templeton World Charity Foundation. J.D. acknowledges support via the European Commission (grant CyGenTig), the Biotechnology and Biological Sciences Research Council (grant BB/M018040/1) and the Medical Research Council (grant MR/R026483/1). The opinions expressed in this publication are those of the authors and do not necessarily reflect the views of the funders.

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  1. Deanery of Biomedical Sciences, and Synthsys Centre for Synthetic Biology, Hugh Robson Building, University of Edinburgh, Edinburgh, UK

    Jamie Davies

  2. Allen Discovery Center at Tufts University, Medford, MA, USA

    Michael Levin

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Davies, J., Levin, M. Synthetic morphology with agential materials. Nat Rev Bioeng 1, 46–59 (2023). https://doi.org/10.1038/s44222-022-00001-9

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