Biomaterials and engineered microenvironments to control YAP/TAZ-dependent cell behaviour

Abstract

Mechanical signals are increasingly recognized as overarching regulators of cell behaviour, controlling stemness, organoid biology, tissue development and regeneration. Moreover, aberrant mechanotransduction is a driver of disease, including cancer, fibrosis and cardiovascular defects. A central question remains how cells compute a host of biomechanical signals into meaningful biological behaviours. Biomaterials and microfabrication technologies are essential to address this issue. Here we review a large body of evidence that connects diverse biomaterial-based systems to the functions of YAP/TAZ, two highly related mechanosensitive transcriptional regulators. YAP/TAZ orchestrate the response to a suite of engineered microenviroments, emerging as a universal control system for cells in two and three dimensions, in static or dynamic fashions, over a range of elastic and viscoelastic stimuli, from solid to fluid states. This approach may guide the rational design of technological and material-based platforms with dramatically improved functionalities and inform the generation of new biomaterials for regenerative medicine applications.

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Fig. 1: Microfabrication and biomaterial designs and YAP/TAZ regulation.
Fig. 2: Dynamic preservation of stem cells in organoid outgrowths requires ‘conforming’ properties of biomaterials.
Fig. 3: Biomaterials mimicking altered microenvironments in human diseases.

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Acknowledgements

The authors thank all members of the S.P. laboratory for discussion. This work is supported by AIRC Special Program Molecular Clinical Oncology ‘5 per mille’, by an AIRC PI-Grant, by a MIUR-FARE grant to S.P., and by Epigenetics Flagship project CNR-MIUR grants to S.P. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 670126-DENOVOSTEM).

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Brusatin, G., Panciera, T., Gandin, A. et al. Biomaterials and engineered microenvironments to control YAP/TAZ-dependent cell behaviour. Nature Mater 17, 1063–1075 (2018). https://doi.org/10.1038/s41563-018-0180-8

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