Engineered Living Materials: From artificial membrane binding proteins to 3D bioprinted tissue constructs

Host: Professor Leonie Quinn

Abstract

Reengineering cells to operate proactively in unnatural biological environments invariably involves the assembly of multiple components, which can only be integrated when compatible interfaces are built into the design. In practice, this can be achieved through the synthesis of hybrid materials comprising highly cooperative biological and synthetic parts that can be used to attenuate cell-host tissue interactions, drive protein self-assembly, and provide rudimentary extracellular matrices for 3D bioprinting. The systems methodology that underpins this design approach provides a gateway to the development of non-traditional approaches to tissue engineering and regenerative medicine. Accordingly, I describe an emerging research programme that spans the fields of synthetic biology, biomaterials, and regenerative medicine. Here, artificial cell plasma membrane binding protein constructs are synthesised using a two-step process: protein supercharging to give a supercationic species; followed by the electrostatic assembly of a polymer surfactant corona. Significantly, the resulting constructs spontaneously assemble at the plasma membrane of human mesenchymal stem cells, providing resistance to hypoxia during tissue engineering.^1,2 Moreover, the methodology can be readily adapted to display a modified thrombin on stems cell, giving rise to self-contained plasma membrane nucleated hydrogels,³ or utilised to produce bacterial adhesin fusion constructs that direct stem cells to the myocardium.⁴

Biography

Adam Perriman is a Professor of Bioengineering and UKRI Future Leaders Fellow, who recently relocated to Australia to take up a joint Professorial position between the JCSMR and RSC. He is also founder and director of the Bristol Centre for Bioprinting (University of Bristol, UK). He is internationally distinguished for his pioneering research on the construction of novel synthetic biomolecular systems, and his research interests span the fields of biophysics, synthetic biology and tissue engineering. His contributions to this field of interdisciplinary science led to him being named a Wellcome Trust Frontiers Innovator in 2015, and in 2016, he was awarded the British Biophysical Society Young Investigator's Award and Medal. In 2019, he was named a UK Research and Innovation Future Leaders Fellow. In 2017 he founded the cell therapy spinout biotech company CytoSeek, which has raised in excess of $10M.

Professor Perriman completed his PhD at the Research School of Chemistry (ANU) in 2007, under the supervision of Prof. John White before moving to the School of Chemistry at the University of Bristol for postdoc with Prof. Steve Mann. After two years he was awarded an EPSRC Interfaces Research Fellowship, which was followed by an EPSRC Early Career Fellowship, which he took up at the School of Cellular and Molecular Medicine in 2013.

His research into the development of novel biomaterials is frequently featured in top-tier journals, including Nature Chemistry, Nature Communications, the Journal of the American Chemical Society and Advanced Materials. This has generated extensive media coverage and has been featured nationally in RSC’s Chemistry World, The Chemical Engineer, New Scientist, and internationally in Nature, Nature Chemistry and Chemical and Engineering News (C&EN). This research also led to nationally-broadcast interviews on BBC4.

References

1. Armstrong, J. P. K.; Shakur, R.; Horne, J. P.; Dickinson, S. C.; Armstrong, C. T.; Lau, K.; Kadiwala, J.; Lowe, R.; Seddon, A.; Mann, S.; Anderson, J. L. R.; Perriman, A. W.; Hollander, A. P., Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue. Nature Communications 2015, 6.

2. Wang, Y., Zoneff, E. R., Thomas, J. W., Hong, N., Tan, L. L., McGillivray, D. J., Perriman, A. W., Law, K. C. L., Thompson, L. H., Moriarty, N., Parish, C. L., Williams, R. J., Jackson, C. J., Nisbet, D. R. Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands. Nature Communications 2023, 14.

3. Deller, R. C.; Richardson, T.; Richardson, R.; Bevan, L.; Zampetakis, I.; Scarpa, F.; Perriman, A. W., Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation. Nature Communications 2019, 10.

4. Xiao, W. J.; Green, T. I. P.; Liang, X. W.; Delint, R. C.; Perry, G.; Roberts, M. S.; Le Vay, K.; Back, C. R.; Ascione, R.; Wang, H. L.; Race, P. R.; Perriman, A. W., Designer artificial membrane binding proteins to direct stem cells to the myocardium. Chemical Science 2019, 10 (32), 7610-7618.