The construction of synthetic cells, or protocells, from non-living molecules represents one of the grand challenges in modern science, bridging the gap between inanimate matter and living systems. While significant progress has been made in enhancing the biochemical complexity of individual protocells, the controlled assembly of these building blocks into functional tissue-like materials—termed prototissues or protocellular materials (PCMs)—remains largely unexplored. PROTOMAT seeks to pioneer advancements in this emerging frontier by integrating synthetic chemistry, materials science, microfluidics, and tissue engineering to design adaptive prototissues capable of mimicking living tissues and interacting with biological cells.
PROTOMAT aims to develop PCMs with three key functionalities:(1) mechanical properties resembling soft living tissues, (2) adaptive and self-regulating behaviours, and (3) the ability to integrate with living cells. These goals address critical gaps in bottom-up synthetic biology, where current research has focused primarily on individual protocells rather than their organized integration into materials with collective behaviour.
The project builds on the Principal Investigator's foundational work, including adhesive proteinosome-based prototissues capable of muscle-like contractions (Nature Materials, 2018) and centimetre-scale PCMs with complex 3D architectures (Advanced Materials, 2021). PROTOMAT extends these findings through three interlinked Research Themes:
1. RT1: Advancing Mechanical Properties – Engineering prototissues with tuneable elastic moduli (1 kPa–1 MPa) to match soft tissues like brain, muscle, and epithelial cells using protocells with synthetic polymeric cytoskeletons assembled via microfluidics.
2. RT2: Higher-Order Behaviours – Pioneering light-responsive prototissues capable of converting luminous stimuli into mechanical motions and biochemical feedback, such as regulating enzymatic activity through photo-induced structural changes.
3. RT3: Integration with Living Cells – Creating hybrid systems where prototissues deliver mechanical and chemical cues to living cells, functionalizing PCM surfaces with cell-adhesion peptides, studying mechanochemical signalling, and developing symbiotic systems where PCMs feed cells and/or protect them from toxins.
The expected impact of PROTOMAT is profound. By bridging non-living and living matter, the project generates foundational knowledge for synthetic biology, enabling the design of "active materials" with applications in regenerative medicine, soft robotics, and biosensing. The high-risk/high-gain nature of the research is mitigated by the PI's expertise, preliminary results, and interdisciplinary approach.
In summary, PROTOMAT aims to transform our understanding of life-like materials, offering innovative solutions to unmet needs in healthcare and biotechnology while pushing the boundaries of synthetic biology. The project's interdisciplinary framework ensures its outcomes will resonate across scientific disciplines, fostering collaborations at the life/non-life interface.
