Intracellular Controlled Radical Polymerizations
Lead Research Organisation:
Technical University of Darmstadt
Department Name: Chemistry
Abstract
The interface of synthetic biology and (bio)materials is a highly promising, yet underexplored field of research. It can play a key role in addressing one of the biggest questions to mankind, which is how life started and how non-living materials became living. If synthetic polymers are successfully integrated into living cells, it will become feasible to induce effects within cells by bio-orthogonal triggers, thereby, opening up new avenues to gain control over cells, i.e. over their development and behavior.
The overarching goal of this project is to integrate biocatalytic controlled radical polymerizations (bioCRP) into living cells as a fundamentally new approach to interface biological systems with synthetic polymers and polymeric nanostructures. This project aims to achieve a fundamental understanding of what happens when amphiphilic block copolymers are synthesized and self-assembled directly within cells, and how this process can be steered to form nanostructures or semi-synthetic cell membranes. To this end, methods for intracellular bioCRP and polymerization-induced self-assembly will be developed and the intracellular self-assembly of block copolymers and their integration into the cell membrane will be studied.
The overarching goal of this project is to integrate biocatalytic controlled radical polymerizations (bioCRP) into living cells as a fundamentally new approach to interface biological systems with synthetic polymers and polymeric nanostructures. This project aims to achieve a fundamental understanding of what happens when amphiphilic block copolymers are synthesized and self-assembled directly within cells, and how this process can be steered to form nanostructures or semi-synthetic cell membranes. To this end, methods for intracellular bioCRP and polymerization-induced self-assembly will be developed and the intracellular self-assembly of block copolymers and their integration into the cell membrane will be studied.
Publications
Belluati A
(2023)
Self-decorating cells via surface-initiated enzymatic controlled radical polymerization.
in Nanoscale
Belluati A
(2024)
Artificial cell synthesis using biocatalytic polymerization-induced self-assembly.
in Nature chemistry
Guo C
(2022)
Peroxidase Activity of Myoglobin Variants Reconstituted with Artificial Cofactors.
in Chembiochem : a European journal of chemical biology
Ornati E
(2025)
Bacteria-Mediated Intracellular Radical Polymerizations.
in Journal of the American Chemical Society
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| EP/V047035/1 | 30/04/2021 | 31/12/2021 | £202,309 | ||
| EP/V047035/2 | Transfer | EP/V047035/1 | 01/02/2022 | 30/05/2023 | £74,652 |
| Description | Enzymatic polymerizations have been implemented into complex biological systems. This includes not only the synthesis of artificial cells by enzymatic synthesis of block copolymers (Belluati et al., Nature Chemistry 2023), but also the enzymatic synthesis of polymers on the surface of yeast cells (Belluati et al., Nanoscale 2023). Furthermore, enzymatic radical polymerizations have also been achieved inside living bacteria cells (Ornati et al., Journal of the American Chemical Society 2025). These key findings show that enzymatic polymerizations can be used to create synthetic materials and their self-assembled nano- and microstructures on and in cells, as well as in the presence of cell lysate, thereby opening up possibilities to tailor living cells with synthetic polymer structures, which blurs the boundary of living and synthetic complex systems. |
| Exploitation Route | Creating synthetic cells or equipping living cells with synthetic polymers could be used to render biotechnological systems more efficient. For example, whole-cell biocatalysts could become more sturdy and, therefore, more efficient in the production of fine chemicals or therapeutics. Moreover, the prepared structures might become interesting for advanced versions of drug delivery, e.g. by producing therapeutic proteins within an artificial cell in situ of a diseased tissue. |
| Sectors | Chemicals Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| URL | https://www.strath.ac.uk/whystrathclyde/news/2023/artificialcellscouldbeusedindrugdelivery/ |
| Description | PhD Studentship to Eleonora Ornati |
| Amount | € 140,198 (EUR) |
| Organisation | Technical University of Darmstadt |
| Sector | Academic/University |
| Country | Germany |
| Start | 01/2022 |
| End | 12/2024 |
| Description | Self-synthesizing, self-organizing, and stimuli-responsive multi-cell-type Engineered Living Materials based on enzymatic polymerizations on cell surfaces (PolyCell-ELMs) |
| Amount | € 281,490 (EUR) |
| Funding ID | 541303355 |
| Organisation | German Research Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 08/2024 |
| End | 08/2027 |
| Title | Artificial cell synthesis using biocatalytic polymerisation-induced self-assembly |
| Description | These are the raw data underlying the pre-print Synthesis of artificial cells via biocatalytic polymerisation-induced self-assembly 10.26434/chemrxiv-2023-c3nhg , to be published in Nature Chemistry (with the updated title Artificial cell synthesis using biocatalytic polymerisation-induced self-assembly) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | Open Data for https://doi.org/10.1038/s41557-023-01391-y |
| URL | https://zenodo.org/record/8414850 |
| Title | Data for: "Peroxidase Activity of Myoglobin Variants Reconstituted with Artificial Cofactors" |
| Description | The data set contains CD spectra, ICP-MS data, native MS data, redox potential measurements, data of enzyme kinetic assays, and UV-vis spectra of the experiments presented and discussed in the Research Article: Guo, C.; Chadwick, R. J.; Foulis, A.; Bedendi, G.; Lubskyy, A.; Rodriguez, K. J.; Pellizzoni, M. M.; Milton, R. D.; Beveridge, R.; Bruns, N.. Peroxidase Activity of Myoglobin Variants Reconstituted with Artificial Cofactors. ChemBioChem 2022, 23, e2022001. https://doi.org/10.1002/cbic.202200197. The data has been deposited as text files or CSV files of the raw data wherever possible. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | Scientific paper ChemBioChem 2022, 23, e2022001. https://doi.org/10.1002/cbic.202200197. |
| URL | https://pureportal.strath.ac.uk/en/datasets/data-for-peroxidase-activity-of-myoglobin-variants-recon... |
| Description | CoM2Life - Convergence Center for Life-Like Soft Materials and Biological Systems |
| Organisation | Johannes Gutenberg University of Mainz |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Com2Life is a research initiative in the framework of the German Excellence Initiative. I am one of the 25 PIs of this project. The full proposal is currently under review. In the preparation of the full proposal, smaller projects were run to prime the pump. |
| Collaborator Contribution | The vision of the CoM2Life initiative is to revolutionize the field of soft biomaterials by integrating principles from living systems into synthetic materials to enable bidirectional communication and continuous interaction with living biological systems. Our approach combines chemistry-centered biomaterials design and synthetic biology-centered design of regulatory circuits, resulting in biomaterials that exhibit life-like properties such as signal sensing, processing, and actuation. This breakthrough towards biomaterials with an 'embodied intelligence' unlocks new possibilities for interactive crossregulation and adaptive co-development in future generations of biomaterials systems. CoM2Life focuses on "deep technology push" concepts to empower biomaterials research with the cutting-edge technologies of tomorrow. These advancements are expected to drive breakthroughs in medical research and personalized healthcare in the coming decades. Examples include feedback-regulated drug delivery, tissue models that can replace animal testing, metabolic regulation systems for tumor immunotherapy, tissue repair, and the engineering of artificial organs. CoM2Life integrates complementary disciplines from JGU Mainz and TU Darmstadt that synergize expertise and technologies, creating a Rhine Main University research hub dedicated to the convergence of living and soft matter disciplines. Our interdisciplinary program equips researchers with a multidisciplinary information advantage to drive future innovation. Experts in communication sciences foster trust and understanding in this highly interdisciplinary environment and develop effective communication strategies to address the challenges of misinformation in the world today. |
| Impact | A publication from the "prime the pump" phase of CoM2Life: https://advanced.onlinelibrary.wiley.com/doi/10.1002/adbi.202400483 |
| Start Year | 2023 |
| Description | CoM2Life - Convergence Center for Life-Like Soft Materials and Biological Systems |
| Organisation | Max Planck Society |
| Department | Max Planck Institute for Polymer Research |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Com2Life is a research initiative in the framework of the German Excellence Initiative. I am one of the 25 PIs of this project. The full proposal is currently under review. In the preparation of the full proposal, smaller projects were run to prime the pump. |
| Collaborator Contribution | The vision of the CoM2Life initiative is to revolutionize the field of soft biomaterials by integrating principles from living systems into synthetic materials to enable bidirectional communication and continuous interaction with living biological systems. Our approach combines chemistry-centered biomaterials design and synthetic biology-centered design of regulatory circuits, resulting in biomaterials that exhibit life-like properties such as signal sensing, processing, and actuation. This breakthrough towards biomaterials with an 'embodied intelligence' unlocks new possibilities for interactive crossregulation and adaptive co-development in future generations of biomaterials systems. CoM2Life focuses on "deep technology push" concepts to empower biomaterials research with the cutting-edge technologies of tomorrow. These advancements are expected to drive breakthroughs in medical research and personalized healthcare in the coming decades. Examples include feedback-regulated drug delivery, tissue models that can replace animal testing, metabolic regulation systems for tumor immunotherapy, tissue repair, and the engineering of artificial organs. CoM2Life integrates complementary disciplines from JGU Mainz and TU Darmstadt that synergize expertise and technologies, creating a Rhine Main University research hub dedicated to the convergence of living and soft matter disciplines. Our interdisciplinary program equips researchers with a multidisciplinary information advantage to drive future innovation. Experts in communication sciences foster trust and understanding in this highly interdisciplinary environment and develop effective communication strategies to address the challenges of misinformation in the world today. |
| Impact | A publication from the "prime the pump" phase of CoM2Life: https://advanced.onlinelibrary.wiley.com/doi/10.1002/adbi.202400483 |
| Start Year | 2023 |
| Description | Enzymatic Polymerization in Aqueous Multi-Phase Systems |
| Organisation | University of Glasgow |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In the collaboration, we study the polymerization activity of enzymes in aqueous multi-phase systems. This will open up new opportunities in the realm of artificial cells and biotechnology. Both collaborators have the expertise of the individual parts of the project, i.e. aqueous multi-phase systems and enzyme partitioning (Schmidt) and enzymatically catalyzed polymerizations (Bruns). |
| Collaborator Contribution | In the collaboration, we study the polymerization activity of enzymes in aqueous multi-phase systems. This will open up new opportunities in the realm of artificial cells and biotechnology. Both collaborators have the expertise of the individual parts of the project, i.e. aqueous multi-phase systems and enzyme partitioning (Schmidt) and enzymatically catalyzed polymerizations (Bruns). |
| Impact | No output yet. |
| Start Year | 2022 |
| Description | PolyCell-ELMs - Self-synthesizing, self-organizing, and stimuli-responsive multi-cell-type Engineered Living Materials based on enzymatic polymerizations on cell surfaces |
| Organisation | Technical University of Darmstadt |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Collaborative research project funded by the DFG together with the group of Prof. Ulrike Nuber (Department of Biology, TU Darmstadt) as part of the SPP 2451 Engineered Living Materials with Adaptive Functions. |
| Collaborator Contribution | Structured multi-cell-type Engineered Living Materials (ELMs) are essential not only for creating responsive and adaptive ELMs but also for creating multicellular formations such as tissues. In such ELMs, polymers can act as a synthetic, tailored extracellular matrix that provides mechanical support to the cell-containing material and initiates and/or maintains cell adhesion and various other functions. Importantly, the polymers between the cells offer the potential to make these ELMs responsive to stimuli. To achieve multicellular, responsive, structured, and reconfigurable formations, we develop ELMs based on yeast and mammalian cells that can self-synthesize synthetic stimuli-responsive polymers on their surface. The polymers are grafted to the cell surface by enzymatic radical polymerizations and act as a selective and reversible scaffold to mediate cell-material-cell adhesion, thus functioning as a stimuli-responsive synthetic analog of an extracellular matrix. |
| Impact | No outputs and outcomes yet. The project is interdisciplinary together with a cell biology group. |
| Start Year | 2024 |
| Description | TU Darmstadt Centre for Synthetic Biology |
| Organisation | Technical University of Darmstadt |
| Department | Department of Biology |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | I have become a member (PI) of the Centre for Synthetic Biology at the Technical University opf Darmstadt (https://www.tu-darmstadt.de/synbio/synbio/mitglieder_1/index.en.jsp), and thus my research activities in the field of polymer-cell hybrid systems, as funded through this EPSRC grant, contribute to the research of the collaborative research centre. |
| Collaborator Contribution | The interdisciplinary centre integrates expertise from the faculties of biology, chemistry and electrical engineering and information technology, material sciences and physics, mechanical engineering and social sciences. Synthetic biology is an engineering approach to equip biological cells with new molecular properties and features. In contrast to conventional biotechnology, this functionality is achieved by combining well-characterised and standardised components at the molecular level. New molecular biology methods, such as versions of the CRISPR gene scissors, are used in the process. Simultaneously, our ability to design RNA molecules and proteins for specific targets is rapidly evolving. In an abstract sense, synthetic biology thus combines defined elements to create a novel technological substrate that allows functional realisation for highly diverse purposes. The possible applications cover a very wide range: intelligent biosensors for in vitro or point-of-care diagnostics, the production of complex chemical compounds, the production of optimised proteins, e.g. enzymes, new (biocompatible) materials, new regulatory mechanisms for more robust plants and microorganisms and the generation of electrical energy. Within the Centre research is distributed over 3 levels: 1. molecular level (DNA, RNA, protein, nanopores) 2. cellular level (gene regulatory circuits, sensing, metabolic engineering) 3. multicellular level (synthetic organs, 3D-bioprinting) |
| Impact | First reserach collaboration with other members of the Centre for Synthetic Biology have started, and have also lead to secure first internal funding (See Funding Research Field Matter and Materials: "Packaging bioactive molecules in artificial particles for controlled cellular effects"; PI: Prof. Ulrike Nuber, Co-PIs: Prof. Nico Bruns, Prof. Annette Andrieu-Brunsen) |
| Start Year | 2022 |