Synthetic Cells With Chemo‐Optical Signaling Enable Targeted Capture and Killing of Bacteria

ABSTRACT Synthetic cells are molecularly defined systems which recreate life‐like behaviors, yet their capacity to engage and act on living cells remains limited. Here, we engineer synthetic cells that combine optical and chemical signaling to achieve programmable capture and killing of bacteria with high spatial precision. To enable bacteria capture, giant unilamellar vesicles (GUVs) were functionalized with the blue light responsive protein BcLOV4, allowing light activatable adhesion to bacterial membranes. Encapsulation of Nanoluciferase allows the synthetic cells to generate an internal bioluminescent light signal, which activates BcLOV4 mediated bacterial recruitment without external illumination. For subsequent bacterial elimination, galactose oxidase was used to generate hydrogen peroxide locally at the GUV membranes, resulting in the selective killing of captured bacteria. This two‐step mechanism mimics a key aspect of innate immune cells, namely localized pathogen elimination, and provides a blueprint for spatially precise antimicrobial synthetic cells.