Synthetic morphology: a powerful tool for future tissue engineering?

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Elise Cachat, Weijia Liu, Kim Martin & Jamie A. Davies

University of Edinburgh, United Kingdom

In developing embryos, the appearance of highly organized structures such as vessels, branches, cell sheets etc. relies on the succession/repetition of a small number of basic morphogenetic events. These processes, occurring in a specific and controlled sequence, are: adhesion, cell locomotion, apoptosis, cell fusion, epithelial-to mesenchymal or mesenchymal-to-epithelial transition, cell sorting, etc. Together with cell differentiation and proliferation, those fundamental mechanisms allow populations of cells to organize themselves into defined geometries and structures as embryos develop into complex organisms. With synthetic biology, we can program mammalian cells to perform such mechanisms by designing genetic circuits, combining various morphogenetic effectors under the control of distinct logic modules. To this purpose, we constructed a modular library of morphogenetic driver genes inducing adhesion, locomotion, fusion, apoptosis and growth arrest. We are first testing these parts individually in different mammalian cell lines to check their ability to induce the desired morphological changes. The active effectors are then tested under the control of various logic gates in selected cell lines. This way, we aim at combining sequences of morphogenetic effectors in a series of proof-of-concept trials for “synthetic morphology”, where cells are genetically programmed to organize themselves into designed 2-D or 3-D structures from artificial external stimuli. Reproducing basic morphogenetic processes in vitro will allow us to test existing theories of developmental biology away from the complex environment of the embryo. Importantly, the resulting cell arrangements are not restricted to natural ones and un-natural, designed structures can be obtained and may, in the future, be used in surgery and regenerative medicine, making synthetic morphology a powerful tool for tissue engineering.