Bottom-up synthetic biology is an emerging field of research in between biology and chemistry aiming to understand how life emerges from an assembly of molecules interacting with each other. In order to do this, scientists in the last decade have created a vast range of synthetic cells, or protocells, from scratch using synthetic materials, or a combination of them with biomolecules. While most of the efforts to date were focused on the advancement of the biochemical complexity of the single protocells, some groups have started exploring how to assemble large numbers of protocells together to generate biomimetic materials capable of emulating living tissues. This interdisciplinary research approach is providing invaluable advances in various fields, such as regenerative medicine, soft robotics and micro-engineering.
Various methodologies have been developed to assemble different synthetic protocell models into interconnected three-dimensional (3D) networks capable of displaying emergent properties. Despite the remarkable progress, most of these methods still face a number of challenges, including the use of complex or lengthy methods to assemble protocells together, and the short shelf lives of the tissue-like materials obtained with these techniques. These materials are also often limited in size and are not free-standing. The successful construction of robust, free-standing tissue-like materials of any size and shape and with simple techniques could be of great importance for tissue engineering and soft robotics.
To address the above challenges, a team of researchers led by Dr Pierangelo Gobbo at the University of Bristol has developed a simple method to assemble millions of protocells into artificial tissues capable of communicating with each other as well as with their external environment. The innovative method, called the “floating mold technique”, allowed the team to create free-standing materials, called “protocellular materials” (PCMs) of any size and shape. It also allowed for the assembly of patterned and layered protocellular materials through the careful arrangement of different types of protocells. Their main objective was to provide a new bottom-up synthetic biology paradigm for future biomimetic materials engineering. Their research work is currently published on Advanced Materials.
In their approach, instead of using 3D printing, acoustic standing waves or magnetic fields to assemble protocells in space like most previous studies, the authors adopted a simple method using PTFE molds to assemble protocells together into sheets of any shape and size. The adhesion between the protocells within the PCMs was obtained by the use of bio-orthogonal chemistry. The protocells were synthesized in order to display chemical groups on their surfaces enabling to undergo click reactions and bind covalently with complementary protocells. The stability of the resulting PCMs in water and their corresponding emergent properties were investigated.
The authors findings demonstrated the unique characteristics of the PCMs fabricated via the new technique. Besides exhibiting remarkable stability in water, the PCMs could communicate both internally and with the external environments. For the first time, 2D periodic arrays of PCMs were fabricated via this method. The team then programmed the bio-reactivity of the protocellular materials so that when waves of chemicals were sent into the environment, the group of protocells responded collectively and it was possible to extract important physical and chemical information from the reaction. For instance, this could lead to a new method to study how a drug moves and distributes inside living tissues. Furthermore, the authors noted the method could be possibly applied to assemble specific protocell phenotypes into biomimetic organoids for drug distribution, delivery of biomolecules and to facilitate biocatalytic synthetic tasks.
In summary, University of Bristol developed a novel bottom-up methodology for the programmed assembly of protocells into tissue-like materials to address several existing challenges in bottom-up synthetic biology. The resulting materials exhibited unique stability, communication and sensing properties. Overall, the feasibility of the proposed methodology was successfully validated. This approach will pave the way for the fabrication of robust and macroscale tissue-like materials with emergent properties that can interact with living tissues and cells to influence cell growth or provide targeted therapies, for instance. These artificial tissues could also work as organoids to closely replicate in vivo environments for drug screenings and reducing animal testing. The tissues could also be used to assemble the next generation of soft robots fueled by chemicals available in the environment. In a statement to Advances in Engineering, Dr Pierangelo Gobbo added: “The assembly of protocells into large scale protocellular materials displaying emerging bio-sensing capabilities is unprecedented. This achievement represents an important milestone towards the construction of autonomous and adaptive artificial tissues. Our next goal is to advance the biochemical capabilities of our protocellular materials to target important applications in tissue engineering, personalized therapy, pharmacokinetics, micro-bioreactor technologies, and soft robotics.”
Galanti, A., Moreno‐Tortolero, R., Azad, R., Cross, S., Davis, S., & Gobbo, P. (2021). A Floating Mold Technique for the Programmed Assembly of Protocells into Protocellular Materials Capable of Non‐Equilibrium Biochemical Sensing. Advanced Materials, 33(24), 2100340.