Self-synthesizing, self-organizing, and stimuli-responsive multi-cell-type Engineered Living Materials based on enzymatic polymerizations on cell surfaces (PolyCell-ELMs)

• Applicants: Professor Dr. Nico Bruns; Professorin Dr. Ulrike Nuber
• Subject Area: Polymer Materials ; Developmental Biology ; Synthesis and Properties of Functional Materials ; Preparatory and Physical Chemistry of Polymers
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 541303355

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 propose to develop ELMs based on cells that can self-synthesize synthetic stimuli-responsive polymers on their surface. The polymers will be grafted to the cell surface and will 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. Importantly, our approach will allow the synthesis and deposition of a very thin synthetic extracellular matrix analog at the single-cell level, thereby introducing a new method to control cellular self-organization in 3D tissue formation. In addition, our approach will also overcome the current limitations of intentionally placing different human cell types in close proximity to each other that would otherwise segregate spontaneously within 3D cultures. Unlike natural extracellular matrices, the polymer properties, such as polarity as well as cell adhesion moieties, will be switchable by temperature and light. When changing from a hydrophobic to a more hydrophilic polymer, the interactions between the polymer-wrapped cells become weak, allowing the cells to rearrange into any new multicellular shape. Furthermore, in the state of weak polymer-polymer interactions, the cells can be resuspended into a growth medium, allowing continued growth of the biomass under optimal oxygen and nutrient conditions without being limited by mass transfer into the bulk of an ELM. Cell growth will be followed by another polymerization step to encapsulate the newly formed cells in the stimuli-responsive polymers. Finally, another aggregation and molding step will allow the production of a living material with a new shape and higher mass than the starting material. Thus, the proposed project will open the door to reconfigurable, self-synthesizing cell-polymer hybrids, thus introducing new concepts for the design, growth, and fabrication of adaptive ELMs and tissue mimics with enhanced cellular survival and multicellular spatial arrangement.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2451: Engineered Living Materials with Adaptive Functions
• Co-Investigator: Dr. Andrea Belluati