Communication between natural and artificial cells
 

Cell-to-cell communication is a vital property of all living multicellular organisms. In order to understand how this process can be mimicked and controlled precisely, we have engineered a hybrid natural-artificial cell system. This system utilizes an ATP-mediated transduction mechanism for bidirectional communication between natural dendritic cells and stimuli-responsive polymer-based artificial cells. The energy uptake in the form of ATP released from natural cells was used for driving enzymatic bioluminescent reactions in polymersomes. In turn, ATP was enzymatically-generated in polymersomes and released on cue to dendritic cells acting as a signalling mechanism for metabolic stimulation.

A research team led by Prof. Katharina Landfester at the Max Planck Institute for Polymer Research developed a hybrid system of natural cells interacting with artificial cells to drive molecular exchange in a controlled manner. The polymersomes used as artificial cells were specifically engineered to be robust and biocompatible in cellular environments for long-term coculture with natural cells.

In order to control the communication pathway, a UV-responsive molecule was integrated into the artificial cell membrane. The increased permeability allowed the transfer of energy in the form of ATP bidirectionally in and out of the artificial cell. The molecular exchange was showcased by triggering complex coacervation within the artificial cells.

The UV-responsive polymersomes were used as enzymatic reactors, generating bioluminescence after the uptake of ATP released by natural cells. Thereby, the polymersome system was established as an energy sensing platform being capable of indicating increased cell lysis in integrated hybrid cell populations.

Furthermore, a communication from polymersomes to natural cell was established using these artificial cells as bioreactors for continuous ATP generation. This was achieved via an enzymatic reaction producing ATP which was then selectively released to the cells via short UV irradiation. The released ATP led to the detection of increased calcium levels in natural cells, indicating the activated state of the immune cells.

These findings were published in Advanced Functional Materials, showcasing a robust platform for dynamic cell-material interaction and controlled biochemical communication, advancing artificial and living cell integration toward engineered signalling interfaces and programmable bio-hybrid systems.