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Pierangelo Gobbo is an associate professor of organic chemistry at the University of Trieste in Italy. His research group designs novel biomimetic materials: they design and synthesise functional molecules, polymers and nanomaterials, and use them to generate cell mimics that self-assemble into tissue-like materials. We met with Pierangelo to learn more about his journey in synthetic cell research, his approach and his current projects.

He started working on protocells and prototissues with Stephen Mann

“I did my PhD with Professor Mark S. Workentin at the University of Western Ontario in Canada. I worked on synthesising nanomaterials and functionalising their surfaces, to make them adhesive. I used bio-orthogonal reactions for this, which are very efficient reactions and work well in complex environments like inside cells.

“I wanted to continue my academic career, so I contacted Professor Stephen Mann, who, at that time, had just begun working on the design of protocells or synthetic cells. I moved to the UK to join his group at the University of Bristol. Together, we used bio-orthogonal chemistry to design reactive protocells capable of adhering to each other and forming synthetic prototissue spheroids*.

“When I set up my own research group, first in Bristol and then in Trieste (Italy), I continued to work on the concept of protocell assemblies. I developed a method for growing macroscopic prototissue sheets instead of small spheroids. These sheets can now be fabricated in sizes of a few square centimetres, with well-defined shapes and complex 3D architectures.”

*Spheroid: tissue composed of protocells assembled in a spheroidal structure

What are synthetic cells, protocells and prototissues?
“As a chemist, I see synthetic cells or protocells as micro-compartments that function in conditions far from thermodynamic equilibrium. In other words, they function only in the presence of the right chemical fuel or under the right conditions.
“A prototissue is an  organized assembly of protocells that work together to achieve a higher goal: the emergence of collective behaviour that they do not have individually.”

He focuses on the synergy between chemistry and the mechanics of materials.

“Living cells are sensitive to the mechanical properties of their environment. Some cells like to grow on stiff surfaces, others prefer soft ones, like hydrogels. Some other cells, like diaphragm cells, need a continuous dynamic mechanical stimulus.

“To bridge the gap between physical and biological sciences, we need to connect chemical reactivity and the physics and mechanics of the material itself. For example, producing a chemical reaction that is transduced into contraction and allows a synthetic cell to move.

“My group and I are working on this synergy between the chemistry and mechanics of materials. For example, we recently developed a photo-mechano-chemical transduction system. The prototissue we formed could sense its surroundings and react to a specific chemical, triggering an internal enzymatic cascade reaction. But we coupled this system with a light-activated contractility movement. When the light turned on, it triggered a mechanical contraction that blocked the enzymatic reaction.”

In 2022, he received an ERC Starting Grant. This was the first funding of its kind (Horizon Europe) for the University of Trieste. The PROTOMAT project seeks to develop self-assembling prototissues capable of integrating and interacting with living cells, both chemically and mechanically.

“ERC grants are very difficult to obtain, so getting one was a huge achievement for me. It changed my life. It helped me set up my group and allowed me to lead a big research project.

“PROTOMAT is at the interface between non-living and living matter. We want to establish communication between protocell and living cells, based on a chemical signal and the synergy between the chemical reaction and the mechanics of the material.”

Pierangelo’s research is mainly driven by curiosity…

“We must investigate fundamental questions. My chemist’s soul pushes me to see if we can build synthetic cells and tissues from scratch, using only non-biological components. This is not a biomimetic approach. It is a bio-inspired approach, inspired by functionality.

“Our perception of life is closely tied to what we can observe here on Earth. But we don’t really know if life is much more than that. Could there be cells living in the methane lakes of Titan, Saturn’s moon? Would their membranes be made of phospholipids or something completely different? With this mindset, we can explore fundamental questions about the chemistry of life. For instance, we can use non-biological components to design life-like materials that can withstand extreme conditions, like high temperatures and very acidic environments, and ‘live’ where biological systems can’t. This opens up possibilities that biology alone simply can’t achieve.”

… but he also works on practical applications with companies

“We have a responsibility to those who have funded us, to translate our work into technology. Industry can turn our knowledge into useful applications. It can also inspire us with new ideas. My group is working with Enphos s.r.l., a company in the energy sector. Thanks to Enphos, we came up with the idea of using our protocells to produce fuels like hydrogen.

“Dialogue between academia and industry can be difficult. We researchers live in a kind of fairy tale, driven by curiosity to explore new things, while people in the industry face concrete problems and can’t always speak freely.

“It’s key to improve communication between researchers and companies. This way, we can support each other. Good dialogue helps us understand their goals and methods and can reveal why they are reluctant to try something else. This understanding allows us to offer better advice on alternative solutions.”

If you would like to learn more about Pierangelo and his research, visit the Gobbo Group website or contact him directly and start a conversation!