Mechano-responsive synthetic cells to engineer the immune response

There is a growing perspective whereby the function of biological systems is dependent on their mechanical properties and their ability to generate mechanical forces. This is true of immune cells, whose internal force generating machinery; the cell cytoskeleton, is essential to their function. At the same time, an improved understanding of the immune system holds huge promise towards its use as a therapeutic, whereby engineering our own immune system will enable more effective treatment of cancers. Realising this potential relies on accelerating our understanding of how mechanical forces regulate immune cell function. In the proposed work, we will develop synthetic cells based on hydrogel microspheres that mimic the physical properties of antigen presenting cells. Via their interaction with immune cells, the synthetic cells can systemically informing how specific physical properties, such as stiffness, regulate immune cell function. Furthermore, we will engineer our synthetic cells such that they are able to report on forces generated by the immune cells and respond to the application of force via biochemical signalling. In this way, force generation intrinsic to immune cell function can be harnessed to release signalling molecules that can in turn influence immune cell function. By engineering such mechanically induced feedback loops, we will investigate the potential of engineering immune cell function within the tumour micro-environment. Consequently, the proposed work will provide key insights into how the function of immune cells depends on mechanical forces, and provide a means of exploiting mechano-regulation to augment and tune immune cell function toward novel therapies.