Integrating non-living and living matter via protocellular materials (PCMs) design and synthetic construction

The bottom-up construction of synthetic cells or protocells from inanimate molecules and materials is one of the grand challenges of our time. While research thus far has been focused on increasing the biochemical complexity individual protocells, this research proposal intends to pioneer the first scientific advancements towards the controlled assembly of protocell building blocks into forms of adaptive and self-regulating protocellular materials (PCMs) that can integrate with living cells and target their mechanochemical sensory pathways.To achieve this, I am proposing to work at the interface of synthetic chemistry, materials science, microfluidics, and tissue engineering to address the following unprecedented aspects of PCM design and synthetic construction: (1) the engineering of PCMs with mechanical properties that mimic those of soft living tissues; (2) the engineering of PCMs with rudimentary adaptive and self-regulating higher-order behaviours; and (3) the development PCMs capable of interacting and integrating with living cells. I will start by developing the first experimental methodologies to assemble PCMs with a range of elastic moduli that mimic those of soft living tissues from protocells endowed with synthetic polymeric cytoskeletons of different composition. I will then engineer the first adaptive PCMs capable of autonomously converting environmental luminous stimuli into mechanical motions and reconfigurations that will self-regulate their endogenous enzymatic reactivity. Finally, I will develop the first forms of PCMs capable of delivering both mechanical and biochemical cues for living cell spreading, proliferation and differentiation in vitro.Overall, the proposed work will pioneer new internationally leading science at the life/non-life interface that will generate transformative ideas in the field of bottom-up synthetic biology with profound fundamental and applied consequences, especially in tissue engineering and regenerative medicine.