Self-assembly of hybrid 3D cultures by integrating living and synthetic cells.

Piernitzki N., Gao N., Gasparoni G., Krauß LM., Schulze-Hentrich J., Dustin M., Schrul B., Győrffy B., Mann S., Staufer O.

Self-assembly is a fundamental property of living matter that drives the three-dimensional organization of cell collectives such as tissues and organs. Here, the co-assembly of synthetic and natural cells is leveraged to create hybrid living 3D cancer cultures. We screen a range of synthetic cell models for their ability to form augmented tumoroids with artificial but controllable micro-environments, and show that the balance of inter- and extracellular adhesion and synthetic cell surface tension are key material properties driving integrated co-assembly. We demonstrate that synthetic cells based on droplet-supported lipid bilayers can establish artificial tumor immune microenvironments (ART-TIMEs), mimicking immunogenic signals within tumoroids and eliminating the need to integrate complex living immune cells. Using the ART-TIME approach, we identify a AhR-ARNT-mediated co-signaling mechanism between PD-1 and CD2 as a driver in immune evasion of pancreatic ductal adenocarcinoma. Our study advances the field of hybrid organoid engineering, offers opportunities for the construction and modelling of artificial tumour environments, and marks a step towards the design of functional living/non-living cytomimetic materials.

DOI

10.1038/s41467-025-66789-3

Type

Journal article

Publication Date

2025-12-10T00:00:00+00:00

Volume

16

Keywords

Humans, Tumor Microenvironment, Cell Line, Tumor, Organoids, Artificial Cells, Cell Culture Techniques, Three Dimensional, Lipid Bilayers, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Signal Transduction

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