Microfluidic Assembly of Synthetic Tissues from Synthetic Cells

Abstract

Biological tissues demonstrate emergent properties arising from the collective interactions of individual cells. While developmental biology has revealed the molecular mechanisms that control processes such as cell-cell adhesion, cellular rearrangements, and mechanosignalling, understanding how the local interactions lead to tissue scale mechanics remains challenging due to the biochemical complexity of living systems. Minimal synthetic tissue models allow us to isolate and examine the underlying physical principles. Liposomes as synthetic cells provide a biomimetic platform with tunable membrane characteristics and the ability to assemble into more complex structures. We present minimal tissue mimetic models based on synthetic cells that enable quantification to link microscale interactions to macroscale features in minimal synthetic tissues. To facilitate these studies, we have optimized the solvent mediated dewetting method to produce some of the highest throughput. This high yield enabled us to develop tissue mimetic structures in two complementary configurations: a freestanding monolayer and a confined microfluidic assembly. Morphological analysis in freestanding model revealed that adhesion-mediated packing induced significant deformation of synthetic cells, accompanied by changes in circularity and eccentricity. The fluorescent assay in confined model demonstrated that adhesive tissue formation reduced transport rates by decreasing pore size and increasing pathway tortuosity while maintaining mechanical stability under flow. Together, these minimal tissue-mimetic platforms provide a quantitative framework for linking synthetic-cell properties, collective organization, and emergent tissue-scale phenomena.