Prof. Adam W. Perriman, UKRI Future Leaders Fellow, Professor of Bioengineering, School of Cellular and Molecular Medicine, University of Bristol, UK    

The Rational Design of Artificial Membrane Binding Proteins for Regenerative Medicine

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 amplify or attenuate cell-host tissue interactions. The systems methodology that underpins this design approach provides a gateway to the development of non-traditional approaches to 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 cartilage tissue engineering.¹ Moreover, the methodology can be readily adapted to display a modified thrombin on stems cell, giving rise to self-contained plasma membrane nucleated hydrogels,² or utilised to produce bacterial adhesin fusion constructs that direct stem cells to the myocardium.³

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. 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.
3. 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.

Host: Associate Professor Menglin Chen, Dept. of Engineering & iNANO, AU